<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/NCT04495283</url>
  </required_header>
  <id_info>
    <org_study_id>CP-NVK009-0005</org_study_id>
    <nct_id>NCT04495283</nct_id>
  </id_info>
  <brief_title>A Phase 2 Study to Evaluate Pregabalin and Acetaminophen Compared to Acetaminophen and Placebo in Subjects Undergoing Bunionectomy</brief_title>
  <official_title>A Phase 2, Randomized, Double-Blind, Placebo- and Comparator-Controlled Trial to Evaluate the Safety and Efficacy of Combination of Pregabalin and Acetaminophen Compared to Acetaminophen and Placebo in Subjects Undergoing Bunionectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nevakar, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Nevakar Injectables, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Nevakar, Inc.</source>
  <oversight_info>
    <has_dmc>No</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>
      A Phase 2, Randomized, Double-Blind, Placebo- and Comparator-Controlled Trial to Evaluate the&#xD;
      Safety and Efficacy of Combination Pregabalin and Acetaminophen Compared to Acetaminophen and&#xD;
      Placebo in Subjects Undergoing Bunionectomy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Phase 2, Randomized, Double-Blind, Placebo- and Comparator-Controlled Trial to Evaluate the&#xD;
      Safety and Efficacy of Combination Pregabalin and Acetaminophen Compared to Acetaminophen and&#xD;
      Placebo in Subjects Undergoing Bunionectomy&#xD;
&#xD;
      Up to 80 subjects will be randomized (32 in each active treatment group, 16 placebo).&#xD;
&#xD;
      To evaluate the efficacy of combination pregabalin (PGB) and acetaminophen (APAP)&#xD;
      administered vs. placebo for pain control in subjects undergoing bunionectomy.&#xD;
&#xD;
      The placebo will be the saline solution.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 28, 2020</start_date>
  <completion_date type="Actual">November 12, 2020</completion_date>
  <primary_completion_date type="Actual">November 12, 2020</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>
    <intervention_model_description>Parallel Assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Up to 80 subjects will be randomized (32 in each active treatment group, 16 placebo).&#xD;
Eligible subjects will be randomized on Day 1 in a 2:2:1 ratio to receive either a combination of PGB and APAP administered (Group A), APAP (Group B), or placebo (Group C).</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Summed Pain Intensity (SPI) Between Group A and Group C</measure>
    <time_frame>0 to 48 hours</time_frame>
    <description>Pain Intensity using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with a score between 0-10 (0= no pain; 10 = worst imaginable pain). Summed Pain Intensity (SPI0-48) was calculated using the trapezoidal method as the area under the curve (AUC) of pain intensity as measured using the NRS through various time intervals up to 48 hours. For SPI0-48 calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) from 0 to 48 hours, including any imputed values, was used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI0-48 was calculated using the formula: Sum (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at various time points. This outcome was compared between a combination of PGB and APAP (Group A) and placebo (Group C) from Hour 0 to Hour 48 (SPI0-48)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Summed Pain Intensity (SPI) Compared Between Group A and Group B</measure>
    <time_frame>0 to 48 hours</time_frame>
    <description>Pain Intensity using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with a score between 0-10 (0= no pain; 10 = worst imaginable pain). Summed Pain Intensity (SPI0-48) -was calculated using the trapezoidal method as the area under the curve (AUC) of pain intensity as measured using the NRS through various time intervals up to 48 hours. For SPI0-48 calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) from 0 to 48 hours, including any imputed values, were used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI0-48 was calculated using the formula: SUM (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at various time points. This outcome was compared between a combination of PGB and APAP (Group A) and APAP alone (Group B) from Hour 0 to Hour 48 (SPI0-48)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summed Pain Intensity (SPI) Assessed by Numeric Rating Scale From Hour 0 to Hour 12 (SPI0-12), Hour 12 to Hour 24 (SPI12-24), and Hour 24 to Hour 48 (SPI24-48).</measure>
    <time_frame>0, 12, 24, 48 hours</time_frame>
    <description>Pain Intensity was determined using a pain rating of 0-10 on the NRS, with a score between 0-10 (0= no pain; 10 = worst imaginable pain). SPI were calculated using the trapezoidal method as the AUC of pain intensity as measured using the NRS through various time intervals at 0-12, 12-24 and 24-48 hours. For specific time interval SPI calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) in the respective time interval, including any imputed values, were used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI at various time intervals were calculated using the formula: SUM (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at respective time interval (0-12, 12-24 and 24-48 hours). This outcome was compared between a combination of PGB and APAP, APAP alone, and placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summed Pain Intensity (SPI) Assessed by Numeric Rating Scale Over Time</measure>
    <time_frame>0, 1, 2, 4, 6, 8, 10 ,12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, and 48 hours</time_frame>
    <description>Pain Intensity was determined using a pain rating of 0-10 on the NRS, with a score between 0-10 (0= no pain; 10 = worst imaginable pain). SPI were calculated using the trapezoidal method as the AUC of pain intensity as measured using the NRS through various time intervals from 0 hour till each time point at 1, 2, 4, 6, 8, 10 ,12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, and 48 hours. For specific time interval SPI calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) in the respective time interval, including any imputed values, were used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI at various time intervals were calculated using the formula: SUM (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at respective time intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Related Adverse Events (TRAE)</measure>
    <time_frame>7 days</time_frame>
    <description>A TRAE is defined as a treatment-emergent adverse event (TEAE) that was classified by the investigator as related to study drug. The number of participants with TRAE were reported</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Were Opioid Free Over Time</measure>
    <time_frame>12 to 48 hours</time_frame>
    <description>Percentages of participants who did not take opioid (rescue medication) over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Consumption of Opioid Rescue Medication Through 24 Hours and 48 Hours</measure>
    <time_frame>24 hours and 48 hours</time_frame>
    <description>The total consumption of opioid rescue analgesia through 24 hours and through 48 hours was reported</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Consumption of Rescue Medication</measure>
    <time_frame>7 days</time_frame>
    <description>The total consumption of rescue analgesia was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Use of Rescue Medication From Hour 0</measure>
    <time_frame>7 days</time_frame>
    <description>Time to first use of rescue medication from Hour 0 was reported. Hour 0 was defined as the end of surgery (i.e., completion of the last suture).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Used Rescue Medication</measure>
    <time_frame>7 days</time_frame>
    <description>Percentage of participants who used rescue medication is reported</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global Assessment of Pain</measure>
    <time_frame>48 hours</time_frame>
    <description>Patient Global Assessment (PGA) of pain control at 48 hours was reported. Patient global evaluation will be self-reported over 24 hours, using a 0-4 categorical rating scale of: (0) poor, (1) fair, (2) good, (3) very good, and (4) excellent</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Concentration for PGB and APAP</measure>
    <time_frame>Pre-infusion (at least 3.0 minutes before the start of the first infusion) and at 0.5, 1.5, 6.0, 8.0, 12.0, 16.0, 18.0, 24.0, 30.0, 32.0, 36.0, 40.0, 42.0, and 48 hours post-infusion</time_frame>
    <description>The Plasma Concentration (Cmax) is defined as the maximum observed concentration. Multiple blood samples were drawn at pre-decided time points. Timing for blood draws was within 3 minutes of the end of every infusion. Three minutes was the maximum allowance as every effort was made to take the sample as close as possible to 1.0 minute after infusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum Observed Concentration for PGB and APAP</measure>
    <time_frame>Pre-infusion (at least 3.0 minutes before the start of the first infusion) and at 0.5, 1.5, 6.0, 8.0, 12.0, 16.0, 18.0, 24.0, 30.0, 32.0, 36.0, 40.0, 42.0, and 48 hours post-infusion</time_frame>
    <description>The Plasma Concentration (Cmin) is defined as the minimum observed concentration. Multiple blood samples were drawn at pre-decided time points. Timing for blood draws was within 3 minutes of the end of every infusion. Three minutes was the maximum allowance as every effort was made to take the sample as close as possible to 1.0 minute after infusion.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">87</enrollment>
  <condition>Postoperative Pain</condition>
  <arm_group>
    <arm_group_label>PGB and APAP (Group A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>APAP (Group B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (Group C).</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pregabalin</intervention_name>
    <description>Pregabalin is a structural derivative of the inhibitory neurotransmitter gamma aminobutyric acid with anticonvulsant, anxiolytic and sleep-modulating properties.</description>
    <arm_group_label>PGB and APAP (Group A)</arm_group_label>
    <other_name>PGB</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetaminophen</intervention_name>
    <description>Acetaminophen is a non-salicylate antipyretic and non-opioid analgesic agent.</description>
    <arm_group_label>APAP (Group B)</arm_group_label>
    <arm_group_label>PGB and APAP (Group A)</arm_group_label>
    <other_name>APAP</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo 1</intervention_name>
    <description>Placebo for APAP</description>
    <arm_group_label>Placebo (Group C).</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo 2</intervention_name>
    <description>Placebo for combination</description>
    <arm_group_label>APAP (Group B)</arm_group_label>
    <arm_group_label>Placebo (Group C).</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provide informed consent by signing the informed consent form (ICF) approved by the&#xD;
             Institutional Review Board (IRB);&#xD;
&#xD;
          -  Be male or female aged 18-65 years;&#xD;
&#xD;
          -  Be scheduled to undergo unilateral first metatarsal bunionectomy;&#xD;
&#xD;
          -  Be in good health and capable of undergoing a bunionectomy under anesthesia as&#xD;
             described in the study surgical and anesthetic protocol;&#xD;
&#xD;
          -  Weigh between 50 and 100 kg (body mass index [BMI] &lt;32 kg/m2);&#xD;
&#xD;
          -  Have no additional planned surgeries other than bunionectomy during the course of the&#xD;
             study;&#xD;
&#xD;
          -  Have negative urine drug screen for drugs indicative of illicit drug use (unless&#xD;
             results can be explained by a current prescription or acceptable over-the-counter&#xD;
             medication at screening as determined by the investigator) and no detectable results&#xD;
             on the alcohol test (breath or saliva) indicative of alcohol abuse at screening,&#xD;
             and/or prior to surgery (may be repeated if the Investigator suspects a false-positive&#xD;
             result). Note: For those subjects who test positive for tetrahydrocannabinol (THC), if&#xD;
             they are willing to abstain from use or consumption of THC-containing products from&#xD;
             screening through end of the subject's participation in the study, they may be allowed&#xD;
             to participate in the study.&#xD;
&#xD;
          -  Biological female subjects must be non-lactating, sterile (bilateral tubal ligation,&#xD;
             bilateral salpingectomy, or hysterectomy), post-menopausal for at least 2 years, have&#xD;
             a partner that is sterile, be abstinent, use a highly effective double- contraception&#xD;
             method (hormonal protection is insufficient), or use an FDA-approved contraceptive for&#xD;
             greater than 2 months prior to the screening visit and commit to an acceptable form of&#xD;
             birth control for the duration of the study and for 30 days after completion of the&#xD;
             study;&#xD;
&#xD;
          -  Be willing and able to complete the study procedures and pain scales and communicate&#xD;
             meaningfully in English with study personnel.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have a medical condition or history that in the Investigator's opinion could adversely&#xD;
             impact the subject's participation or safety or the conduct of the study, or interfere&#xD;
             with the pain assessments, including the following:&#xD;
&#xD;
               1. Serious breathing difficulties or respiratory risk factors (including use of&#xD;
                  opioid pain medicines and other drugs that depress the central nervous system),&#xD;
                  and conditions such as chronic obstructive pulmonary disease that reduce lung&#xD;
                  function.&#xD;
&#xD;
               2. Hypertension (uncontrolled), cardiovascular disease, or history of&#xD;
                  cerebrovascular events. Hypertension must be controlled without known end organ&#xD;
                  damage.&#xD;
&#xD;
               3. Concurrent painful conditions that may require analgesic treatment during the&#xD;
                  study period.&#xD;
&#xD;
               4. History of significantly reduced hepatic or renal function, angle closure&#xD;
                  glaucoma, or convulsive disorder.&#xD;
&#xD;
               5. Recent history of urinary retention.&#xD;
&#xD;
               6. Opioid tolerant, i.e., the subject is currently taking or has taken a chronic&#xD;
                  opioid at a dose greater than or equal to 20 mg morphine milligram equivalents&#xD;
                  (MME) per day (more than 30 consecutive days of daily use) for pain in the 2&#xD;
                  months prior to surgery.&#xD;
&#xD;
               7. Active cutaneous disease, or other disease, at the surgical site.&#xD;
&#xD;
               8. Peripheral vascular disease, sickle cell disease, vascular grafts, or vasospastic&#xD;
                  disorders.&#xD;
&#xD;
               9. Known bleeding disorder or is taking agents affecting coagulation preoperatively.&#xD;
&#xD;
                  Deep venous thrombosis (DVT) prophylaxis of the surgeon's choice is permitted&#xD;
                  postoperatively.&#xD;
&#xD;
              10. Diabetes mellitus (uncontrolled). Diabetes mellitus must be controlled without&#xD;
                  known end organ damage.&#xD;
&#xD;
              11. History of malignancy in the past 2 years with the exception of squamous cell&#xD;
                  carcinoma or basal cell carcinoma.&#xD;
&#xD;
              12. Prior bunionectomy on the index foot or other foot surgery on the index foot that&#xD;
                  could impact the surgery or data collection endpoints.&#xD;
&#xD;
          -  Use of disallowed medications including the following:&#xD;
&#xD;
               1. Pain medication (opioids, NSAIDs, cyclooxygenase (COX)-2 inhibitors, tramadol,&#xD;
                  ketamine, clonidine, gabapentin, pregabalin, or cannabinoids) within 2 days prior&#xD;
                  to Day 1.&#xD;
&#xD;
               2. Central nervous system (CNS) active drugs such as benzodiazepines, tricyclic&#xD;
                  antidepressants, serotonin and norepinephrine reuptake inhibitors (SNRIs), or&#xD;
                  selective serotonin reuptake inhibitors (SSRIs) for pain within seven days prior&#xD;
                  to Day 1. These drugs are permitted for non-pain indications if the dose has been&#xD;
                  stable for at least 30 days prior to Day 1 and is planned to remain stable&#xD;
                  throughout the study. The use of lorazepam and other sleep medications, except&#xD;
                  those containing analgesic properties, is permitted.&#xD;
&#xD;
               3. Use of parenteral or oral corticosteroid(s) within 14 days prior to Day 1.&#xD;
&#xD;
               4. Antihypertensive agent or diabetic regimen at a dose that has not been stable for&#xD;
                  at least 30 days, or which is not expected to remain stable throughout the study.&#xD;
&#xD;
               5. 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&#xD;
                  throughout the study.&#xD;
&#xD;
          -  Use of warfarin is allowed, at the investigator's discretion, for DVT prophylaxis&#xD;
             after the surgery.&#xD;
&#xD;
          -  Significant history of allergic reactions or known intolerance to pregabalin or any&#xD;
             gabapentinoid, to APAP, to any rescue medication used in the study, or any medication&#xD;
             used in the surgical and anesthetic protocol.&#xD;
&#xD;
          -  Female subjects (biological females only) who are pregnant or lactating, who plan to&#xD;
             get pregnant, or who have a positive serum pregnancy test at Screening or a positive&#xD;
             urine pregnancy test at either Day -1 or Day 1 prior to surgery.&#xD;
&#xD;
          -  Participated in another clinical trial within 30 days, or previously participated in a&#xD;
             clinical study with a similar investigational product.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Lotus Clinical Resarch,LLC</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lotus HD Research</name>
      <address>
        <city>Bellaire</city>
        <state>Texas</state>
        <zip>77401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <results_first_submitted>September 1, 2021</results_first_submitted>
  <results_first_submitted_qc>October 25, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 23, 2021</results_first_posted>
  <last_update_submitted>October 25, 2021</last_update_submitted>
  <last_update_submitted_qc>October 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2021</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>Pregabalin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 19, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT04495283/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from 28 July 2020 till 26 Oct 2020 across the sites.</recruitment_details>
      <pre_assignment_details>Subjects underwent a Screening Visit (Day -42 to Day -2) and were required to sign an informed consent form (ICF) before undertaking any study-specific procedures or assessments. Pre-operative assessments were conducted within 24 hours prior to surgery (on either Day -1 or Day 1 prior to surgery.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>PGB and APAP (Group A)</title>
          <description>Group A receives pregabalin (PGB) plus acetaminophen (APAP) prior to surgery and placebo 1 post-surgery.</description>
        </group>
        <group group_id="P2">
          <title>APAP (Group B)</title>
          <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
        </group>
        <group group_id="P3">
          <title>Placebo (Group C).</title>
          <description>Group C receives placebo 1 prior to surgery and placebo 2 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="35"/>
                <participants group_id="P2" count="35"/>
                <participants group_id="P3" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="34"/>
                <participants group_id="P3" count="14"/>
              </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="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </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="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Safety Analysis Set included all subjects who received any amount of study drug (APAP + PGB, APAP, or placebo), whether or not they were prematurely withdrawn from the study.</population>
      <group_list>
        <group group_id="B1">
          <title>PGB and APAP (Group A)</title>
          <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
        </group>
        <group group_id="B2">
          <title>APAP (Group B)</title>
          <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
        </group>
        <group group_id="B3">
          <title>Placebo (Group C).</title>
          <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery.</description>
        </group>
        <group group_id="B4">
          <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="35"/>
            <count group_id="B2" value="35"/>
            <count group_id="B3" value="17"/>
            <count group_id="B4" value="87"/>
          </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="43.7" spread="13.33"/>
                    <measurement group_id="B2" value="42.1" spread="11.68"/>
                    <measurement group_id="B3" value="43.3" spread="11.98"/>
                    <measurement group_id="B4" value="43.0" spread="12.31"/>
                  </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="25"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="73"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="14"/>
                  </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="9"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="59"/>
                  </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_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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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="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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="62"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.03" spread="3.213"/>
                    <measurement group_id="B2" value="26.55" spread="3.471"/>
                    <measurement group_id="B3" value="26.05" spread="3.406"/>
                    <measurement group_id="B4" value="26.24" spread="3.326"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Summed Pain Intensity (SPI) Between Group A and Group C</title>
        <description>Pain Intensity using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with a score between 0-10 (0= no pain; 10 = worst imaginable pain). Summed Pain Intensity (SPI0-48) was calculated using the trapezoidal method as the area under the curve (AUC) of pain intensity as measured using the NRS through various time intervals up to 48 hours. For SPI0-48 calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) from 0 to 48 hours, including any imputed values, was used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI0-48 was calculated using the formula: Sum (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at various time points. This outcome was compared between a combination of PGB and APAP (Group A) and placebo (Group C) from Hour 0 to Hour 48 (SPI0-48)</description>
        <time_frame>0 to 48 hours</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>Placebo (Group C).</title>
            <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery</description>
          </group>
        </group_list>
        <measure>
          <title>Summed Pain Intensity (SPI) Between Group A and Group C</title>
          <description>Pain Intensity using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with a score between 0-10 (0= no pain; 10 = worst imaginable pain). Summed Pain Intensity (SPI0-48) was calculated using the trapezoidal method as the area under the curve (AUC) of pain intensity as measured using the NRS through various time intervals up to 48 hours. For SPI0-48 calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) from 0 to 48 hours, including any imputed values, was used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI0-48 was calculated using the formula: Sum (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at various time points. This outcome was compared between a combination of PGB and APAP (Group A) and placebo (Group C) from Hour 0 to Hour 48 (SPI0-48)</description>
          <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="153.08" spread="15.238"/>
                    <measurement group_id="O2" value="267.51" spread="21.864"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-114.43</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>26.650</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
            <ci_upper_limit>-80.01</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Summed Pain Intensity (SPI) Compared Between Group A and Group B</title>
        <description>Pain Intensity using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with a score between 0-10 (0= no pain; 10 = worst imaginable pain). Summed Pain Intensity (SPI0-48) -was calculated using the trapezoidal method as the area under the curve (AUC) of pain intensity as measured using the NRS through various time intervals up to 48 hours. For SPI0-48 calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) from 0 to 48 hours, including any imputed values, were used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI0-48 was calculated using the formula: SUM (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at various time points. This outcome was compared between a combination of PGB and APAP (Group A) and APAP alone (Group B) from Hour 0 to Hour 48 (SPI0-48)</description>
        <time_frame>0 to 48 hours</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>APAP (Group B)</title>
            <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Summed Pain Intensity (SPI) Compared Between Group A and Group B</title>
          <description>Pain Intensity using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with a score between 0-10 (0= no pain; 10 = worst imaginable pain). Summed Pain Intensity (SPI0-48) -was calculated using the trapezoidal method as the area under the curve (AUC) of pain intensity as measured using the NRS through various time intervals up to 48 hours. For SPI0-48 calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) from 0 to 48 hours, including any imputed values, were used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI0-48 was calculated using the formula: SUM (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at various time points. This outcome was compared between a combination of PGB and APAP (Group A) and APAP alone (Group B) from Hour 0 to Hour 48 (SPI0-48)</description>
          <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="153.08" spread="15.238"/>
                    <measurement group_id="O2" value="223.24" spread="5.238"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-70.16</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>21.549</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
            <ci_upper_limit>-42.32</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Summed Pain Intensity (SPI) Assessed by Numeric Rating Scale From Hour 0 to Hour 12 (SPI0-12), Hour 12 to Hour 24 (SPI12-24), and Hour 24 to Hour 48 (SPI24-48).</title>
        <description>Pain Intensity was determined using a pain rating of 0-10 on the NRS, with a score between 0-10 (0= no pain; 10 = worst imaginable pain). SPI were calculated using the trapezoidal method as the AUC of pain intensity as measured using the NRS through various time intervals at 0-12, 12-24 and 24-48 hours. For specific time interval SPI calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) in the respective time interval, including any imputed values, were used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI at various time intervals were calculated using the formula: SUM (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at respective time interval (0-12, 12-24 and 24-48 hours). This outcome was compared between a combination of PGB and APAP, APAP alone, and placebo.</description>
        <time_frame>0, 12, 24, 48 hours</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>APAP (Group B)</title>
            <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Group C).</title>
            <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery</description>
          </group>
        </group_list>
        <measure>
          <title>Summed Pain Intensity (SPI) Assessed by Numeric Rating Scale From Hour 0 to Hour 12 (SPI0-12), Hour 12 to Hour 24 (SPI12-24), and Hour 24 to Hour 48 (SPI24-48).</title>
          <description>Pain Intensity was determined using a pain rating of 0-10 on the NRS, with a score between 0-10 (0= no pain; 10 = worst imaginable pain). SPI were calculated using the trapezoidal method as the AUC of pain intensity as measured using the NRS through various time intervals at 0-12, 12-24 and 24-48 hours. For specific time interval SPI calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) in the respective time interval, including any imputed values, were used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI at various time intervals were calculated using the formula: SUM (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at respective time interval (0-12, 12-24 and 24-48 hours). This outcome was compared between a combination of PGB and APAP, APAP alone, and placebo.</description>
          <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SPI 0-12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.09" spread="3.728"/>
                    <measurement group_id="O2" value="49.09" spread="3.728"/>
                    <measurement group_id="O3" value="58.89" spread="5.349"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 12-24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.92" spread="5.082"/>
                    <measurement group_id="O2" value="69.35" spread="5.082"/>
                    <measurement group_id="O3" value="88.95" spread="7.292"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 24-48</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="126.83" spread="13.128"/>
                    <measurement group_id="O2" value="184.33" spread="13.128"/>
                    <measurement group_id="O3" value="221.58" spread="18.837"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Summed Pain Intensity (SPI) Assessed by Numeric Rating Scale Over Time</title>
        <description>Pain Intensity was determined using a pain rating of 0-10 on the NRS, with a score between 0-10 (0= no pain; 10 = worst imaginable pain). SPI were calculated using the trapezoidal method as the AUC of pain intensity as measured using the NRS through various time intervals from 0 hour till each time point at 1, 2, 4, 6, 8, 10 ,12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, and 48 hours. For specific time interval SPI calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) in the respective time interval, including any imputed values, were used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI at various time intervals were calculated using the formula: SUM (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at respective time intervals.</description>
        <time_frame>0, 1, 2, 4, 6, 8, 10 ,12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, and 48 hours</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>APAP (Group B)</title>
            <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Group C).</title>
            <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Summed Pain Intensity (SPI) Assessed by Numeric Rating Scale Over Time</title>
          <description>Pain Intensity was determined using a pain rating of 0-10 on the NRS, with a score between 0-10 (0= no pain; 10 = worst imaginable pain). SPI were calculated using the trapezoidal method as the AUC of pain intensity as measured using the NRS through various time intervals from 0 hour till each time point at 1, 2, 4, 6, 8, 10 ,12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, and 48 hours. For specific time interval SPI calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) in the respective time interval, including any imputed values, were used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI at various time intervals were calculated using the formula: SUM (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at respective time intervals.</description>
          <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</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="35"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SPI 0-1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.26" spread="0.509"/>
                    <measurement group_id="O2" value="0.73" spread="0.870"/>
                    <measurement group_id="O3" value="0.45" spread="0.951"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.26" spread="1.591"/>
                    <measurement group_id="O2" value="2.39" spread="2.539"/>
                    <measurement group_id="O3" value="2.16" spread="2.560"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.63" spread="5.120"/>
                    <measurement group_id="O2" value="8.02" spread="6.703"/>
                    <measurement group_id="O3" value="9.62" spread="6.196"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.68" spread="9.650"/>
                    <measurement group_id="O2" value="17.09" spread="10.606"/>
                    <measurement group_id="O3" value="20.71" spread="10.368"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.00" spread="14.211"/>
                    <measurement group_id="O2" value="28.09" spread="14.266"/>
                    <measurement group_id="O3" value="33.64" spread="14.203"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.25" spread="18.413"/>
                    <measurement group_id="O2" value="38.71" spread="18.140"/>
                    <measurement group_id="O3" value="45.95" spread="18.510"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.09" spread="22.725"/>
                    <measurement group_id="O2" value="49.09" spread="21.692"/>
                    <measurement group_id="O3" value="58.89" spread="21.362"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.12" spread="27.035"/>
                    <measurement group_id="O2" value="58.62" spread="25.009"/>
                    <measurement group_id="O3" value="72.17" spread="24.820"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-16</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.08" spread="30.480"/>
                    <measurement group_id="O2" value="67.98" spread="27.401"/>
                    <measurement group_id="O3" value="84.46" spread="27.487"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.84" spread="33.985"/>
                    <measurement group_id="O2" value="78.49" spread="31.847"/>
                    <measurement group_id="O3" value="97.57" spread="32.420"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-20</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.49" spread="36.259"/>
                    <measurement group_id="O2" value="86.24" spread="35.453"/>
                    <measurement group_id="O3" value="108.32" spread="37.011"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.17" spread="43.864"/>
                    <measurement group_id="O2" value="108.25" spread="43.928"/>
                    <measurement group_id="O3" value="134.91" spread="42.035"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-28</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.94" spread="50.680"/>
                    <measurement group_id="O2" value="128.83" spread="52.561"/>
                    <measurement group_id="O3" value="158.01" spread="45.579"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-32</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.85" spread="56.483"/>
                    <measurement group_id="O2" value="148.93" spread="59.923"/>
                    <measurement group_id="O3" value="180.50" spread="54.648"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-36</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="114.43" spread="63.776"/>
                    <measurement group_id="O2" value="169.44" spread="67.178"/>
                    <measurement group_id="O3" value="203.32" spread="64.342"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-40</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="126.45" spread="69.998"/>
                    <measurement group_id="O2" value="186.70" spread="73.308"/>
                    <measurement group_id="O3" value="224.78" spread="72.951"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-44</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="139.54" spread="78.396"/>
                    <measurement group_id="O2" value="199.95" spread="78.945"/>
                    <measurement group_id="O3" value="246.09" spread="84.178"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPI 0-48</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="153.08" spread="87.398"/>
                    <measurement group_id="O2" value="223.24" spread="91.581"/>
                    <measurement group_id="O3" value="267.51" spread="92.791"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-Related Adverse Events (TRAE)</title>
        <description>A TRAE is defined as a treatment-emergent adverse event (TEAE) that was classified by the investigator as related to study drug. The number of participants with TRAE were reported</description>
        <time_frame>7 days</time_frame>
        <population>The Safety Analysis Set included all subjects who received any amount of study drug (APAP + PGB, APAP, or placebo), whether or not they were prematurely withdrawn from the study. The Safety Analysis Set was used for the summaries and listings of all safety assessments. Subjects were analyzed according to treatment received</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>APAP (Group B)</title>
            <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Group C).</title>
            <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Related Adverse Events (TRAE)</title>
          <description>A TRAE is defined as a treatment-emergent adverse event (TEAE) that was classified by the investigator as related to study drug. The number of participants with TRAE were reported</description>
          <population>The Safety Analysis Set included all subjects who received any amount of study drug (APAP + PGB, APAP, or placebo), whether or not they were prematurely withdrawn from the study. The Safety Analysis Set was used for the summaries and listings of all safety assessments. Subjects were analyzed according to treatment received</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Were Opioid Free Over Time</title>
        <description>Percentages of participants who did not take opioid (rescue medication) over time.</description>
        <time_frame>12 to 48 hours</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>APAP (Group B)</title>
            <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Group C).</title>
            <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Were Opioid Free Over Time</title>
          <description>Percentages of participants who did not take opioid (rescue medication) over time.</description>
          <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>During 12-24 Hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.7"/>
                    <measurement group_id="O2" value="45.7"/>
                    <measurement group_id="O3" value="35.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>During 12-48 Hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.6"/>
                    <measurement group_id="O2" value="28.6"/>
                    <measurement group_id="O3" value="29.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Consumption of Opioid Rescue Medication Through 24 Hours and 48 Hours</title>
        <description>The total consumption of opioid rescue analgesia through 24 hours and through 48 hours was reported</description>
        <time_frame>24 hours and 48 hours</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>APAP (Group B)</title>
            <description>Group B receives placebo 2 prior to surgery and APAP post-surgery</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Group C).</title>
            <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery</description>
          </group>
        </group_list>
        <measure>
          <title>Total Consumption of Opioid Rescue Medication Through 24 Hours and 48 Hours</title>
          <description>The total consumption of opioid rescue analgesia through 24 hours and through 48 hours was reported</description>
          <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
          <units>oral 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="35"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Consumption of Rescue Medication through 24 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.86" spread="14.134"/>
                    <measurement group_id="O2" value="19.24" spread="17.019"/>
                    <measurement group_id="O3" value="28.88" spread="20.981"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Consumption of Rescue Medication through 48 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.36" spread="21.796"/>
                    <measurement group_id="O2" value="33.39" spread="30.847"/>
                    <measurement group_id="O3" value="43.88" spread="32.419"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Consumption of Rescue Medication</title>
        <description>The total consumption of rescue analgesia was reported.</description>
        <time_frame>7 days</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>APAP (Group B)</title>
            <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Group C).</title>
            <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery</description>
          </group>
        </group_list>
        <measure>
          <title>Total Consumption of Rescue Medication</title>
          <description>The total consumption of rescue analgesia was reported.</description>
          <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
          <units>oral 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="35"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.79" spread="22.344"/>
                    <measurement group_id="O2" value="34.24" spread="32.496"/>
                    <measurement group_id="O3" value="44.76" spread="33.609"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Use of Rescue Medication From Hour 0</title>
        <description>Time to first use of rescue medication from Hour 0 was reported. Hour 0 was defined as the end of surgery (i.e., completion of the last suture).</description>
        <time_frame>7 days</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>APAP (Group B)</title>
            <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Group C).</title>
            <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Use of Rescue Medication From Hour 0</title>
          <description>Time to first use of rescue medication from Hour 0 was reported. Hour 0 was defined as the end of surgery (i.e., completion of the last suture).</description>
          <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="28"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.60" lower_limit="5.93" upper_limit="16.12"/>
                    <measurement group_id="O2" value="5.78" lower_limit="4.27" upper_limit="7.97"/>
                    <measurement group_id="O3" value="4.31" lower_limit="3.57" upper_limit="5.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Used Rescue Medication</title>
        <description>Percentage of participants who used rescue medication is reported</description>
        <time_frame>7 days</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>APAP (Group B)</title>
            <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Group C).</title>
            <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Used Rescue Medication</title>
          <description>Percentage of participants who used rescue medication is reported</description>
          <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="35"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.1"/>
                    <measurement group_id="O2" value="80.0"/>
                    <measurement group_id="O3" value="82.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Global Assessment of Pain</title>
        <description>Patient Global Assessment (PGA) of pain control at 48 hours was reported. Patient global evaluation will be self-reported over 24 hours, using a 0-4 categorical rating scale of: (0) poor, (1) fair, (2) good, (3) very good, and (4) excellent</description>
        <time_frame>48 hours</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>APAP (Group B)</title>
            <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Group C).</title>
            <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Global Assessment of Pain</title>
          <description>Patient Global Assessment (PGA) of pain control at 48 hours was reported. Patient global evaluation will be self-reported over 24 hours, using a 0-4 categorical rating scale of: (0) poor, (1) fair, (2) good, (3) very good, and (4) excellent</description>
          <population>The Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study drug. Subjects were analyzed according to the treatment group to which they were randomized.</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="35"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>(0) Poor</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>(1) Fair</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>(2) Good</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>(3) Very good</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>(4) Excellent</title>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Concentration for PGB and APAP</title>
        <description>The Plasma Concentration (Cmax) is defined as the maximum observed concentration. Multiple blood samples were drawn at pre-decided time points. Timing for blood draws was within 3 minutes of the end of every infusion. Three minutes was the maximum allowance as every effort was made to take the sample as close as possible to 1.0 minute after infusion.</description>
        <time_frame>Pre-infusion (at least 3.0 minutes before the start of the first infusion) and at 0.5, 1.5, 6.0, 8.0, 12.0, 16.0, 18.0, 24.0, 30.0, 32.0, 36.0, 40.0, 42.0, and 48 hours post-infusion</time_frame>
        <population>The PK Analysis Set included all randomized subjects who received any amount of study drug, had no protocol deviations affecting the pharmacokinetic (PK) variables, and had sufficient data collected to allow evaluation of least one PK parameter (minimum plasma concentration of the drug [Cmin], Cmax, or both). Subjects were analyzed according to treatment received. All PK analyses were performed using the PK Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>APAP (Group B)</title>
            <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Group C).</title>
            <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Concentration for PGB and APAP</title>
          <description>The Plasma Concentration (Cmax) is defined as the maximum observed concentration. Multiple blood samples were drawn at pre-decided time points. Timing for blood draws was within 3 minutes of the end of every infusion. Three minutes was the maximum allowance as every effort was made to take the sample as close as possible to 1.0 minute after infusion.</description>
          <population>The PK Analysis Set included all randomized subjects who received any amount of study drug, had no protocol deviations affecting the pharmacokinetic (PK) variables, and had sufficient data collected to allow evaluation of least one PK parameter (minimum plasma concentration of the drug [Cmin], Cmax, or both). Subjects were analyzed according to treatment received. All PK analyses were performed using the PK Analysis Set</population>
          <units>nanogram per milliliter (ng/ml)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mean Cmax Values of Pregabalin- First Dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10068" spread="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean Cmax Values of Pregabalin- Last Dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12960" spread="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean Cmax Values of Acetaminophen-First Dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                    <count group_id="O2" value="33"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28700" spread="34"/>
                    <measurement group_id="O2" value="16847" spread="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Minimum Observed Concentration for PGB and APAP</title>
        <description>The Plasma Concentration (Cmin) is defined as the minimum observed concentration. Multiple blood samples were drawn at pre-decided time points. Timing for blood draws was within 3 minutes of the end of every infusion. Three minutes was the maximum allowance as every effort was made to take the sample as close as possible to 1.0 minute after infusion.</description>
        <time_frame>Pre-infusion (at least 3.0 minutes before the start of the first infusion) and at 0.5, 1.5, 6.0, 8.0, 12.0, 16.0, 18.0, 24.0, 30.0, 32.0, 36.0, 40.0, 42.0, and 48 hours post-infusion</time_frame>
        <population>The PK Analysis Set included all randomized subjects who received any amount of study drug, had no protocol deviations affecting the PK variables, and had sufficient data collected to allow evaluation of least one PK parameter (minimum plasma concentration of the drug [Cmin], Cmax, or both). Subjects were analyzed according to treatment received. All PK analyses were performed using the PK Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>PGB and APAP (Group A)</title>
            <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
          </group>
          <group group_id="O2">
            <title>APAP (Group B)</title>
            <description>Group B receives placebo 2 prior to surgery and APAP post-surgery.</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Group C).</title>
            <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery.</description>
          </group>
        </group_list>
        <measure>
          <title>Minimum Observed Concentration for PGB and APAP</title>
          <description>The Plasma Concentration (Cmin) is defined as the minimum observed concentration. Multiple blood samples were drawn at pre-decided time points. Timing for blood draws was within 3 minutes of the end of every infusion. Three minutes was the maximum allowance as every effort was made to take the sample as close as possible to 1.0 minute after infusion.</description>
          <population>The PK Analysis Set included all randomized subjects who received any amount of study drug, had no protocol deviations affecting the PK variables, and had sufficient data collected to allow evaluation of least one PK parameter (minimum plasma concentration of the drug [Cmin], Cmax, or both). Subjects were analyzed according to treatment received. All PK analyses were performed using the PK Analysis Set</population>
          <units>nanogram per milliliter (ng/ml)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Aside from the pre-dose sample collected just before the start of the first dose, there were no samples taken prior to each dose. Therefore, Cmin was unable to be estimated from the available samples.</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Aside from the pre-dose sample collected just before the start of the first dose, there were no samples taken prior to each dose. Therefore, Cmin was unable to be estimated from the available samples.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 7 days (± 1 day)</time_frame>
      <desc>An adverse event (AE) is defined as any untoward medical occurrence and does not necessarily have to have causal relationship with the study medication. An AE can therefore be an unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease, which is a change from baseline and is temporally associated with the use of the study medication, whether or not it is considered related to the study medication.</desc>
      <group_list>
        <group group_id="E1">
          <title>PGB and APAP (Group A)</title>
          <description>Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.</description>
        </group>
        <group group_id="E2">
          <title>APAP (Group B)</title>
          <description>Group B receives placebo 2 prior to surgery and APAP post-surgery</description>
        </group>
        <group group_id="E3">
          <title>Placebo (Group C).</title>
          <description>Group C receives placebo 1 prior to surgery and placebo 2 post-surgery</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="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA Version 23.0</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="27" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </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="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Application site rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Infusion site extravasation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Injection site extravasation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Post procedural cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Transaminases abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Euphoric mood</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </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 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>Eric Lang, MD</name_or_title>
      <organization>Nevakar, Inc.</organization>
      <phone>(908) 367-7400</phone>
      <email>Clinicaltrials@nevakar.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/NCT04495283
org study id: CP-NVK009-0005
nct id: NCT04495283
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
A Phase 2, Randomized, Double-Blind, Placebo- and Comparator-Controlled Trial to Evaluate the
      Safety and Efficacy of Combination Pregabalin and Acetaminophen Compared to Acetaminophen and
      Placebo in Subjects Undergoing Bunionectomy
A Phase 2, Randomized, Double-Blind, Placebo- and Comparator-Controlled Trial to Evaluate the
      Safety and Efficacy of Combination Pregabalin and Acetaminophen Compared to Acetaminophen and
      Placebo in Subjects Undergoing Bunionectomy

      Up to 80 subjects will be randomized (32 in each active treatment group, 16 placebo).

      To evaluate the efficacy of combination pregabalin (PGB) and acetaminophen (APAP)
      administered vs. placebo for pain control in subjects undergoing bunionectomy.

      The placebo will be the saline solution.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Up to 80 subjects will be randomized (32 in each active treatment group, 16 placebo).
Eligible subjects will be randomized on Day 1 in a 2:2:1 ratio to receive either a combination of PGB and APAP administered (Group A), APAP (Group B), or placebo (Group C).
measure: Summed Pain Intensity (SPI) Between Group A and Group C
time frame: 0 to 48 hours
description: Pain Intensity using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with a score between 0-10 (0= no pain; 10 = worst imaginable pain). Summed Pain Intensity (SPI0-48) was calculated using the trapezoidal method as the area under the curve (AUC) of pain intensity as measured using the NRS through various time intervals up to 48 hours. For SPI0-48 calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) from 0 to 48 hours, including any imputed values, was used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI0-48 was calculated using the formula: Sum (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at various time points. This outcome was compared between a combination of PGB and APAP (Group A) and placebo (Group C) from Hour 0 to Hour 48 (SPI0-48)
measure: Summed Pain Intensity (SPI) Compared Between Group A and Group B
time frame: 0 to 48 hours
description: Pain Intensity using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with a score between 0-10 (0= no pain; 10 = worst imaginable pain). Summed Pain Intensity (SPI0-48) -was calculated using the trapezoidal method as the area under the curve (AUC) of pain intensity as measured using the NRS through various time intervals up to 48 hours. For SPI0-48 calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) from 0 to 48 hours, including any imputed values, were used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI0-48 was calculated using the formula: SUM (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at various time points. This outcome was compared between a combination of PGB and APAP (Group A) and APAP alone (Group B) from Hour 0 to Hour 48 (SPI0-48)
measure: Summed Pain Intensity (SPI) Assessed by Numeric Rating Scale From Hour 0 to Hour 12 (SPI0-12), Hour 12 to Hour 24 (SPI12-24), and Hour 24 to Hour 48 (SPI24-48).
time frame: 0, 12, 24, 48 hours
description: Pain Intensity was determined using a pain rating of 0-10 on the NRS, with a score between 0-10 (0= no pain; 10 = worst imaginable pain). SPI were calculated using the trapezoidal method as the AUC of pain intensity as measured using the NRS through various time intervals at 0-12, 12-24 and 24-48 hours. For specific time interval SPI calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) in the respective time interval, including any imputed values, were used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI at various time intervals were calculated using the formula: SUM (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at respective time interval (0-12, 12-24 and 24-48 hours). This outcome was compared between a combination of PGB and APAP, APAP alone, and placebo.
measure: Summed Pain Intensity (SPI) Assessed by Numeric Rating Scale Over Time
time frame: 0, 1, 2, 4, 6, 8, 10 ,12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, and 48 hours
description: Pain Intensity was determined using a pain rating of 0-10 on the NRS, with a score between 0-10 (0= no pain; 10 = worst imaginable pain). SPI were calculated using the trapezoidal method as the AUC of pain intensity as measured using the NRS through various time intervals from 0 hour till each time point at 1, 2, 4, 6, 8, 10 ,12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, and 48 hours. For specific time interval SPI calculation, all available NRS pain intensity scores (scheduled pain intensity, unscheduled pain intensity and pre-rescue pain intensity) in the respective time interval, including any imputed values, were used in the calculation. Hour 0 was defined as the time of the end of surgery. SPI at various time intervals were calculated using the formula: SUM (1/2 (SPIi + SPIi+1)*Δt), where Δt was the time difference between Time i and Time (i+1). The represented values are sum of pain intensity scores at respective time intervals.
measure: Number of Participants With Treatment-Related Adverse Events (TRAE)
time frame: 7 days
description: A TRAE is defined as a treatment-emergent adverse event (TEAE) that was classified by the investigator as related to study drug. The number of participants with TRAE were reported
measure: Percentage of Participants Who Were Opioid Free Over Time
time frame: 12 to 48 hours
description: Percentages of participants who did not take opioid (rescue medication) over time.
measure: Total Consumption of Opioid Rescue Medication Through 24 Hours and 48 Hours
time frame: 24 hours and 48 hours
description: The total consumption of opioid rescue analgesia through 24 hours and through 48 hours was reported
measure: Total Consumption of Rescue Medication
time frame: 7 days
description: The total consumption of rescue analgesia was reported.
measure: Time to First Use of Rescue Medication From Hour 0
time frame: 7 days
description: Time to first use of rescue medication from Hour 0 was reported. Hour 0 was defined as the end of surgery (i.e., completion of the last suture).
measure: Percentage of Participants Who Used Rescue Medication
time frame: 7 days
description: Percentage of participants who used rescue medication is reported
measure: Patient Global Assessment of Pain
time frame: 48 hours
description: Patient Global Assessment (PGA) of pain control at 48 hours was reported. Patient global evaluation will be self-reported over 24 hours, using a 0-4 categorical rating scale of: (0) poor, (1) fair, (2) good, (3) very good, and (4) excellent
measure: Maximum Observed Concentration for PGB and APAP
time frame: Pre-infusion (at least 3.0 minutes before the start of the first infusion) and at 0.5, 1.5, 6.0, 8.0, 12.0, 16.0, 18.0, 24.0, 30.0, 32.0, 36.0, 40.0, 42.0, and 48 hours post-infusion
description: The Plasma Concentration (Cmax) is defined as the maximum observed concentration. Multiple blood samples were drawn at pre-decided time points. Timing for blood draws was within 3 minutes of the end of every infusion. Three minutes was the maximum allowance as every effort was made to take the sample as close as possible to 1.0 minute after infusion.
measure: Minimum Observed Concentration for PGB and APAP
time frame: Pre-infusion (at least 3.0 minutes before the start of the first infusion) and at 0.5, 1.5, 6.0, 8.0, 12.0, 16.0, 18.0, 24.0, 30.0, 32.0, 36.0, 40.0, 42.0, and 48 hours post-infusion
description: The Plasma Concentration (Cmin) is defined as the minimum observed concentration. Multiple blood samples were drawn at pre-decided time points. Timing for blood draws was within 3 minutes of the end of every infusion. Three minutes was the maximum allowance as every effort was made to take the sample as close as possible to 1.0 minute after infusion.
arm group label: PGB and APAP (Group A)
arm group type: Experimental
description: Group A receives PGB plus APAP prior to surgery and placebo 1 post-surgery.
arm group label: APAP (Group B)
arm group type: Experimental
description: Group B receives placebo 2 prior to surgery and APAP post-surgery.
arm group label: Placebo (Group C).
arm group type: Experimental
description: Group C receives placebo 1 prior to surgery and placebo 2 post-surgery.
intervention type: Drug
intervention name: Pregabalin
description: Pregabalin is a structural derivative of the inhibitory neurotransmitter gamma aminobutyric acid with anticonvulsant, anxiolytic and sleep-modulating properties.
arm group label: PGB and APAP (Group A)
other name: PGB
intervention type: Drug
intervention name: Acetaminophen
description: Acetaminophen is a non-salicylate antipyretic and non-opioid analgesic agent.
arm group label: APAP (Group B)
arm group label: PGB and APAP (Group A)
other name: APAP
intervention type: Other
intervention name: Placebo 1
description: Placebo for APAP
arm group label: Placebo (Group C).
intervention type: Other
intervention name: Placebo 2
description: Placebo for combination
arm group label: APAP (Group B)
arm group label: Placebo (Group C).
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pain, Postoperative
mesh term: Acetaminophen
mesh term: Pregabalin
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 