<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/NCT03254459</url>
  </required_header>
  <id_info>
    <org_study_id>INS005-17-111</org_study_id>
    <nct_id>NCT03254459</nct_id>
  </id_info>
  <brief_title>Study of Buprenorphine Sublingual Spray Versus Standard of Care Narcotic Therapy for the Treatment of Post-Operative Pain</brief_title>
  <official_title>A Phase 2, Randomized, Open Label, Multiple-Dose, Comparator, Parallel-Group, Safety and Tolerance Study of Buprenorphine Sublingual Spray (0.5 mg TID) Versus Standard of Care Post-Operative Narcotic Therapy for the Treatment of Post-Operative Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>INSYS Therapeutics Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>INSYS Therapeutics Inc</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the safety and tolerability based on the incidence of adverse&#xD;
      experiences of buprenorphine sublingual spray (0.5 milligrams [mg] three times daily [TID])&#xD;
      compared with standard post-operative narcotic therapy in participants with postoperative&#xD;
      pain. Standard post-operative narcotic therapy is defined as morphine intravenous (IV)&#xD;
      injection (4 mg TID) followed by oxycodone hydrochloride tablet (10 mg TID).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 12, 2017</start_date>
  <completion_date type="Actual">November 13, 2017</completion_date>
  <primary_completion_date type="Actual">November 13, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (TEAEs)</measure>
    <time_frame>Days 1 to 8</time_frame>
    <description>An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. A TEAE is an AE with onset that occurs after receiving study drug.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Provided Rescue Medication for Nausea</measure>
    <time_frame>Days 1 to7</time_frame>
    <description>Zofran was used at the clinician's discretion as rescue medication for nausea.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Use of Rescue Medication for Nausea Following Each Dose of the Investigational Product (IP)</measure>
    <time_frame>Days 1 to 7</time_frame>
    <description>Zofran was used at the clinician's discretion as rescue medication for nausea. Time &quot;0&quot; is defined as the time of the administration of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Use of Rescue Medication for Nausea Over 0 to 24 Hours, Over 0 to 48 Hours, Over 0-72 Hours and 0-7 Days</measure>
    <time_frame>0 to 24 hours, 0 to 48 hours, 0 to 72 hours and 0 to 7 days</time_frame>
    <description>Zofran was used at the clinician's discretion as rescue medication for nausea. The total use of rescue medication was calculated for the following 4 time-frames: 0 to 24 hours, 0 to 48 hours, 0 to 72 hours and 0 to 7 days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulse Oximetry Levels at 90 Minutes,12, 24, 48 and 72 Hours</measure>
    <time_frame>90 Minutes,12, 24, 48 and 72 Hours</time_frame>
    <description>Pulse oximetry is a non-invasive method to measure a person's oxygen saturation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Abnormal Electrocardiograms (ECGs) Findings at 90 Minutes,12, 24, 48 and 72 Hours</measure>
    <time_frame>Pre-dose and 90 minutes, 12, 24, 48 and 72 hours after first dose</time_frame>
    <description>A standard 12-lead ECG will be performed after the participant is in the supine (lying face up) position for 5 minutes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Abnormal Oral Cavity Examinations</measure>
    <time_frame>Pre-dose and 90 minutes, 12, 24, 48 and 72 hours after first dose on Days 1 to 4 and End of Study Day 8</time_frame>
    <description>Study staff will perform a sublingual (under the tongue) assessment, noting the color of mucosa and whether inflammation is present.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Pain, Postoperative</condition>
  <arm_group>
    <arm_group_label>Buprenorphine Sublingual Spray 0.5 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Buprenorphine Sublingual Spray 0.5 milligrams (mg) three times a day (TID) for 7 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care Narcotic Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Morphine intravenous (IV), 4 mg TID for 24 hours, followed by oxycodone hydrochloride tablet, 10 mg TID for 6 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Buprenorphine Sublingual Spray</intervention_name>
    <description>0.5 mg Sublingual Spray</description>
    <arm_group_label>Buprenorphine Sublingual Spray 0.5 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <description>4 mg Intravenous Injection</description>
    <arm_group_label>Standard of Care Narcotic Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxycodone Hydrochloride</intervention_name>
    <description>10 mg tablet</description>
    <arm_group_label>Standard of Care Narcotic Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zofran</intervention_name>
    <description>4 mg oral disintegrating tablet (ODT) or IV injection given at the investigator's discretion for nausea</description>
    <arm_group_label>Buprenorphine Sublingual Spray 0.5 mg</arm_group_label>
    <arm_group_label>Standard of Care Narcotic Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Is able to speak and understand the language in which the study is being conducted, is&#xD;
             able to understand and comply with the procedures and study requirements, and has&#xD;
             voluntarily signed and dated an informed consent form approved by an Institutional&#xD;
             Review Board before the conduct of any study procedure.&#xD;
&#xD;
          2. Is a male or female ≥18 and ≤65 years of age.&#xD;
&#xD;
          3. Scheduled for elective bunionectomy, breast augmentation (in women only), or&#xD;
             abdominoplasty.&#xD;
&#xD;
          4. Is classified using the American Society of Anesthesiologists Physical Status&#xD;
             Classification System as P1 to P2.&#xD;
&#xD;
          5. If female, is either not of childbearing potential (defined as postmenopausal for at&#xD;
             least 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy,&#xD;
             or hysterectomy]) or practicing one of the following medically acceptable methods of&#xD;
             birth control:&#xD;
&#xD;
               1. Hormonal methods such as oral, implantable, injectable, vaginal ring, or&#xD;
                  transdermal contraceptives for a minimum of 1 full cycle (based on the&#xD;
                  participant's usual menstrual cycle period) before study drug administration;&#xD;
&#xD;
               2. Total abstinence from sexual intercourse since the last menses before study drug&#xD;
                  administration;&#xD;
&#xD;
               3. Intrauterine device; OR&#xD;
&#xD;
               4. Double-barrier method (condoms, sponge, or diaphragm with spermicidal jellies or&#xD;
                  cream).&#xD;
&#xD;
          6. Has a body weight ≥45 kilograms (kg) and a body mass index (BMI) ≤40 kg/m^2.&#xD;
&#xD;
          7. Is willing and able to comply with study requirements (including diet, alcohol, and&#xD;
             smoking restrictions), complete evaluations and diary, remain at the study site for&#xD;
             ≥72 hours, and return for follow up Day 8 + 2 days after surgery.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Has a known history of allergic reaction or clinically significant intolerance to&#xD;
             acetaminophen, aspirin, opioids, or any nonsteroidal anti-inflammatory drugs (NSAIDs);&#xD;
             history of NSAID-induced bronchospasm (participants with the triad of asthma, nasal&#xD;
             polyps, and chronic rhinitis are at greater risk for bronchospasm and should be&#xD;
             considered carefully); or hypersensitivity, allergy, or significant reaction to sulfa&#xD;
             (including sulfonamide) medicines, ingredients of the study drug, or any other drugs&#xD;
             used in the study, including anesthetics and antibiotics that may be required on the&#xD;
             day of surgery.&#xD;
&#xD;
          2. Has experienced any surgical complications or other issues that, in the investigator's&#xD;
             opinion, could compromise the participant's safety if he or she continues into&#xD;
             randomized treatment or could confound the results of the study.&#xD;
&#xD;
          3. Has a known or suspected history of alcoholism or drug abuse or misuse within 2 years&#xD;
             of Screening or evidence of opioid tolerance or physical dependence before dosing with&#xD;
             the study drug.&#xD;
&#xD;
          4. Has any clinically significant unstable cardiac, respiratory, neurological,&#xD;
             immunological, hematological, or renal disease, or any other condition that, in the&#xD;
             investigator's opinion, could compromise the participant's welfare, ability to&#xD;
             communicate with the study staff, or otherwise contraindicate study participation.&#xD;
&#xD;
          5. Has long QT Syndrome, a family history of long QT Syndrome, or is taking Class IA or&#xD;
             Class III antiarrhythmic medications&#xD;
&#xD;
          6. Has a history or current diagnosis of a significant psychiatric disorder that, in the&#xD;
             investigator's opinion, would affect the participant's ability to comply with the&#xD;
             study requirements.&#xD;
&#xD;
          7. Has tested positive either on the urine drug screen or on the alcohol Breathalyzer&#xD;
             test. Participants who test positive at Screening only and can produce a prescription&#xD;
             in their name from their physician for the medication producing the positive test may&#xD;
             be considered for study enrollment at the investigator's discretion. However, they&#xD;
             must test negative on the day of the surgery.&#xD;
&#xD;
          8. Has a history of a clinically significant (in the investigator's opinion)&#xD;
             gastrointestinal (GI) event within 6 months before Screening or has any history of&#xD;
             peptic or gastric ulcers or GI bleeding.&#xD;
&#xD;
          9. Has an active infection, mucositis, cold sores, viral lesions, local irritation, or in&#xD;
             the investigator's opinion has significant periodontal disease of the oral cavity. In&#xD;
             addition, recent (within 1 year) piercing of the tongue or anywhere in the oral&#xD;
             cavity.&#xD;
&#xD;
         10. Has a surgical or medical condition of the GI or renal system that, in the&#xD;
             investigator's opinion, might significantly alter the absorption, distribution, or&#xD;
             excretion of any drug substance.&#xD;
&#xD;
         11. Is considered by the investigator, for any reason (including, but not limited to, the&#xD;
             risks described as precautions, warnings, and contraindications in the current version&#xD;
             of the investigator's brochure for Buprenorphine Sublingual Spray), to be an&#xD;
             unsuitable candidate to receive the study drug.&#xD;
&#xD;
         12. Is receiving systemic chemotherapy, has an active malignancy of any type, or has been&#xD;
             diagnosed with cancer within 5 years before Screening (excluding squamous or basal&#xD;
             cell carcinoma of the skin).&#xD;
&#xD;
         13. Is currently receiving anticoagulants (eg, heparin or warfarin). Low-dose aspirin for&#xD;
             cardioprotection is allowed.&#xD;
&#xD;
         14. Has used drugs known to be a strong inhibitor or inducer of CYP3A4 within 1 week&#xD;
             before surgery.&#xD;
&#xD;
         15. Has received a course of systemic corticosteroids (either oral or parenteral) within 1&#xD;
             month before Screening (inhaled nasal steroids and topical corticosteroids are&#xD;
             allowed).&#xD;
&#xD;
         16. Has a history of chronic use (defined as daily use for &gt;2 weeks) of NSAIDs, opiates,&#xD;
             or glucocorticoids (except inhaled nasal steroids and topical corticosteroids) within&#xD;
             1 month before study drug administration. Aspirin at a daily dose of ≤325 mg is&#xD;
             allowed for cardiovascular prophylaxis if the participant has been on a stable dose&#xD;
             regimen for ≥30 days before Screening and has not experienced any relevant medical&#xD;
             problem.&#xD;
&#xD;
         17. Has a significant renal or hepatic disease, as indicated by clinical laboratory&#xD;
             assessment (results ≥3 × the upper limit of normal [ULN] for any liver function test,&#xD;
             including aspartate aminotransferase, alanine aminotransferase, and lactate&#xD;
             dehydrogenase, or creatinine ≥1.5 × ULN).&#xD;
&#xD;
         18. Has any clinically significant laboratory or 12-lead electrocardiogram finding at&#xD;
             Screening that in the investigator's opinion contraindicates study participation.&#xD;
&#xD;
         19. Has screening systolic blood pressure ≥160 mmHg and diastolic blood pressure &gt;100 mmHg&#xD;
             (may be repeated one additional time after 5 minutes rest to verify). The investigator&#xD;
             may, at his discretion, choose to exclude participants with hypertensive levels lower&#xD;
             than these if he deems it in the best interest of the participant.&#xD;
&#xD;
         20. Has a history of sleep apnea or other obstructive airway disease.&#xD;
&#xD;
         21. Has a history of nausea and vomiting with buprenorphine products.&#xD;
&#xD;
         22. Has significant difficulties swallowing capsules or is unable to tolerate oral&#xD;
             medication.&#xD;
&#xD;
         23. Previously participated in another clinical study of Buprenorphine Sublingual Spray or&#xD;
             received any investigational drug or device or investigational therapy within 30 days&#xD;
             before Screening.&#xD;
&#xD;
        Post-surgical eligibility requirements:&#xD;
&#xD;
        The participant will be assessed for the following postoperative eligibility criteria&#xD;
&#xD;
          1. Participants must be awake, breathing spontaneously without significant respiratory&#xD;
             depression.&#xD;
&#xD;
          2. Participants must not be actively vomiting or complaining of severe nausea.&#xD;
&#xD;
          3. Participants must be able to answer questions and follow commands.&#xD;
&#xD;
          4. Participants must not have surgical complications that could compromise safety of the&#xD;
             participant or confound the results of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Giovanni DeCastro</last_name>
    <role>Study Director</role>
    <affiliation>INSYS Therapeutics Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lotus Clinical Research, LLC</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Epic Medical Research</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <results_first_submitted>September 25, 2018</results_first_submitted>
  <results_first_submitted_qc>September 25, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">October 29, 2018</results_first_posted>
  <last_update_submitted>September 25, 2018</last_update_submitted>
  <last_update_submitted_qc>September 25, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 29, 2018</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>Morphine</mesh_term>
    <mesh_term>Oxycodone</mesh_term>
    <mesh_term>Buprenorphine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 2, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT03254459/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 8, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT03254459/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Standard of Care Narcotic Therapy</title>
          <description>Morphine intravenous (IV), 4 mg TID for 24 hours, followed by oxycodone hydrochloride tablet, 10 mg TID for 6 days.&#xD;
Morphine: Morphine&#xD;
Oxycodone Hydrochloride: Oxycodone Hydrochloride 10 mg tablet</description>
        </group>
        <group group_id="P2">
          <title>Buprenorphine Sublingual Spray 0.5 mg</title>
          <description>Buprenorphine Sublingual Spray 0.5 milligrams (mg) three times a day (TID) for 7 days.&#xD;
Buprenorphine Sublingual Spray: Buprenorphine Sublingual Spray 0.5 mg</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject Consent</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Miscellaneous</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Standard of Care Narcotic Therapy</title>
          <description>Morphine intravenous (IV), 4 mg TID for 24 hours, followed by oxycodone hydrochloride tablet, 10 mg TID for 6 days.&#xD;
Morphine: Morphine&#xD;
Oxycodone Hydrochloride: Oxycodone Hydrochloride 10 mg tablet</description>
        </group>
        <group group_id="B2">
          <title>Buprenorphine Sublingual Spray 0.5 mg</title>
          <description>Buprenorphine Sublingual Spray 0.5 milligrams (mg) three times a day (TID) for 7 days.&#xD;
Buprenorphine Sublingual Spray: Buprenorphine Sublingual Spray 0.5 mg</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="50"/>
            <count group_id="B2" value="50"/>
            <count group_id="B3" value="100"/>
          </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="36.2" spread="10.83"/>
                    <measurement group_id="B2" value="37.1" spread="11.68"/>
                    <measurement group_id="B3" value="36.6" spread="11.22"/>
                  </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="48"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="96"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </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="17"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs)</title>
        <description>An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. A TEAE is an AE with onset that occurs after receiving study drug.</description>
        <time_frame>Days 1 to 8</time_frame>
        <population>Safety population, all participants who received study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care Narcotic Therapy</title>
            <description>Morphine intravenous (IV), 4 mg TID for 24 hours, followed by oxycodone hydrochloride tablet, 10 mg TID for 6 days.&#xD;
Morphine: Morphine&#xD;
Oxycodone Hydrochloride: Oxycodone Hydrochloride 10 mg tablet</description>
          </group>
          <group group_id="O2">
            <title>Buprenorphine Sublingual Spray 0.5 mg</title>
            <description>Buprenorphine Sublingual Spray 0.5 milligrams (mg) three times a day (TID) for 7 days.&#xD;
Buprenorphine Sublingual Spray: Buprenorphine Sublingual Spray 0.5 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs)</title>
          <description>An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. A TEAE is an AE with onset that occurs after receiving study drug.</description>
          <population>Safety population, all participants who received study drug.</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="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Provided Rescue Medication for Nausea</title>
        <description>Zofran was used at the clinician's discretion as rescue medication for nausea.</description>
        <time_frame>Days 1 to7</time_frame>
        <population>Safety population, all participants who received study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care Narcotic Therapy</title>
            <description>Morphine intravenous (IV), 4 mg TID for 24 hours, followed by oxycodone hydrochloride tablet, 10 mg TID for 6 days.&#xD;
Morphine: Morphine&#xD;
Oxycodone Hydrochloride: Oxycodone Hydrochloride 10 mg tablet</description>
          </group>
          <group group_id="O2">
            <title>Buprenorphine Sublingual Spray 0.5 mg</title>
            <description>Buprenorphine Sublingual Spray 0.5 milligrams (mg) three times a day (TID) for 7 days.&#xD;
Buprenorphine Sublingual Spray: Buprenorphine Sublingual Spray 0.5 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Provided Rescue Medication for Nausea</title>
          <description>Zofran was used at the clinician's discretion as rescue medication for nausea.</description>
          <population>Safety population, all participants who received study drug.</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="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Use of Rescue Medication for Nausea Following Each Dose of the Investigational Product (IP)</title>
        <description>Zofran was used at the clinician's discretion as rescue medication for nausea. Time &quot;0&quot; is defined as the time of the administration of study drug.</description>
        <time_frame>Days 1 to 7</time_frame>
        <population>Safety population, all participants who received study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care Narcotic Therapy</title>
            <description>Morphine intravenous (IV), 4 mg TID for 24 hours, followed by oxycodone hydrochloride tablet, 10 mg TID for 6 days.&#xD;
Morphine: Morphine&#xD;
Oxycodone Hydrochloride: Oxycodone Hydrochloride 10 mg tablet</description>
          </group>
          <group group_id="O2">
            <title>Buprenorphine Sublingual Spray 0.5 mg</title>
            <description>Buprenorphine Sublingual Spray 0.5 milligrams (mg) three times a day (TID) for 7 days.&#xD;
Buprenorphine Sublingual Spray: Buprenorphine Sublingual Spray 0.5 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Use of Rescue Medication for Nausea Following Each Dose of the Investigational Product (IP)</title>
          <description>Zofran was used at the clinician's discretion as rescue medication for nausea. Time &quot;0&quot; is defined as the time of the administration of study drug.</description>
          <population>Safety population, all participants who received study drug.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Data could not be calculated as more than 50% of subjects discontinued prior to Day 8.</measurement>
                    <measurement group_id="O2" value="11.25" lower_limit="5.60" upper_limit="23.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Use of Rescue Medication for Nausea Over 0 to 24 Hours, Over 0 to 48 Hours, Over 0-72 Hours and 0-7 Days</title>
        <description>Zofran was used at the clinician's discretion as rescue medication for nausea. The total use of rescue medication was calculated for the following 4 time-frames: 0 to 24 hours, 0 to 48 hours, 0 to 72 hours and 0 to 7 days.</description>
        <time_frame>0 to 24 hours, 0 to 48 hours, 0 to 72 hours and 0 to 7 days</time_frame>
        <population>Safety population, all participants who received study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care Narcotic Therapy</title>
            <description>Morphine intravenous (IV), 4 mg TID for 24 hours, followed by oxycodone hydrochloride tablet, 10 mg TID for 6 days.&#xD;
Morphine: Morphine&#xD;
Oxycodone Hydrochloride: Oxycodone Hydrochloride 10 mg tablet</description>
          </group>
          <group group_id="O2">
            <title>Buprenorphine Sublingual Spray 0.5 mg</title>
            <description>Buprenorphine Sublingual Spray 0.5 milligrams (mg) three times a day (TID) for 7 days.&#xD;
Buprenorphine Sublingual Spray: Buprenorphine Sublingual Spray 0.5 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Total Use of Rescue Medication for Nausea Over 0 to 24 Hours, Over 0 to 48 Hours, Over 0-72 Hours and 0-7 Days</title>
          <description>Zofran was used at the clinician's discretion as rescue medication for nausea. The total use of rescue medication was calculated for the following 4 time-frames: 0 to 24 hours, 0 to 48 hours, 0 to 72 hours and 0 to 7 days.</description>
          <population>Safety population, all participants who received study drug.</population>
          <units>cumulative number of rescue doses</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>0 to 24 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>0 to 48 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>0 to 72 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>0 to 7 days</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42"/>
                    <measurement group_id="O2" value="152"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pulse Oximetry Levels at 90 Minutes,12, 24, 48 and 72 Hours</title>
        <description>Pulse oximetry is a non-invasive method to measure a person's oxygen saturation.</description>
        <time_frame>90 Minutes,12, 24, 48 and 72 Hours</time_frame>
        <population>Safety population, all participants who received study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care Narcotic Therapy</title>
            <description>Morphine intravenous (IV), 4 mg TID for 24 hours, followed by oxycodone hydrochloride tablet, 10 mg TID for 6 days.&#xD;
Morphine: Morphine&#xD;
Oxycodone Hydrochloride: Oxycodone Hydrochloride 10 mg tablet</description>
          </group>
          <group group_id="O2">
            <title>Buprenorphine Sublingual Spray 0.5 mg</title>
            <description>Buprenorphine Sublingual Spray 0.5 milligrams (mg) three times a day (TID) for 7 days.&#xD;
Buprenorphine Sublingual Spray: Buprenorphine Sublingual Spray 0.5 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Pulse Oximetry Levels at 90 Minutes,12, 24, 48 and 72 Hours</title>
          <description>Pulse oximetry is a non-invasive method to measure a person's oxygen saturation.</description>
          <population>Safety population, all participants who received study drug.</population>
          <units>percentage of oxygen saturation</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>90 minutes</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.3" spread="1.99"/>
                    <measurement group_id="O2" value="96.0" spread="2.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.0" spread="1.93"/>
                    <measurement group_id="O2" value="95.8" spread="2.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.9" spread="1.63"/>
                    <measurement group_id="O2" value="96.6" spread="2.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="48"/>
                    <count group_id="O2" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.5" spread="2.01"/>
                    <measurement group_id="O2" value="96.0" spread="2.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.3" spread="1.36"/>
                    <measurement group_id="O2" value="96.2" spread="2.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Abnormal Electrocardiograms (ECGs) Findings at 90 Minutes,12, 24, 48 and 72 Hours</title>
        <description>A standard 12-lead ECG will be performed after the participant is in the supine (lying face up) position for 5 minutes.</description>
        <time_frame>Pre-dose and 90 minutes, 12, 24, 48 and 72 hours after first dose</time_frame>
        <population>Safety population, all participants who received study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care Narcotic Therapy</title>
            <description>Morphine intravenous (IV), 4 mg TID for 24 hours, followed by oxycodone hydrochloride tablet, 10 mg TID for 6 days.&#xD;
Morphine: Morphine&#xD;
Oxycodone Hydrochloride: Oxycodone Hydrochloride 10 mg tablet</description>
          </group>
          <group group_id="O2">
            <title>Buprenorphine Sublingual Spray 0.5 mg</title>
            <description>Buprenorphine Sublingual Spray 0.5 milligrams (mg) three times a day (TID) for 7 days.&#xD;
Buprenorphine Sublingual Spray: Buprenorphine Sublingual Spray 0.5 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Electrocardiograms (ECGs) Findings at 90 Minutes,12, 24, 48 and 72 Hours</title>
          <description>A standard 12-lead ECG will be performed after the participant is in the supine (lying face up) position for 5 minutes.</description>
          <population>Safety population, all participants who received study drug.</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="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="48"/>
                    <count group_id="O2" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                    <count group_id="O2" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Abnormal Oral Cavity Examinations</title>
        <description>Study staff will perform a sublingual (under the tongue) assessment, noting the color of mucosa and whether inflammation is present.</description>
        <time_frame>Pre-dose and 90 minutes, 12, 24, 48 and 72 hours after first dose on Days 1 to 4 and End of Study Day 8</time_frame>
        <population>Safety population, all participants who received study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care Narcotic Therapy</title>
            <description>Morphine intravenous (IV), 4 mg TID for 24 hours, followed by oxycodone hydrochloride tablet, 10 mg TID for 6 days.&#xD;
Morphine: Morphine&#xD;
Oxycodone Hydrochloride: Oxycodone Hydrochloride 10 mg tablet</description>
          </group>
          <group group_id="O2">
            <title>Buprenorphine Sublingual Spray 0.5 mg</title>
            <description>Buprenorphine Sublingual Spray 0.5 milligrams (mg) three times a day (TID) for 7 days.&#xD;
Buprenorphine Sublingual Spray: Buprenorphine Sublingual Spray 0.5 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Oral Cavity Examinations</title>
          <description>Study staff will perform a sublingual (under the tongue) assessment, noting the color of mucosa and whether inflammation is present.</description>
          <population>Safety population, all participants who received study drug.</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="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="46"/>
                    <count group_id="O2" value="45"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Screening to Day 8</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Standard of Care Narcotic Therapy</title>
          <description>Morphine intravenous (IV), 4 mg TID for 24 hours, followed by oxycodone hydrochloride tablet, 10 mg TID for 6 days.&#xD;
Morphine: Morphine&#xD;
Oxycodone Hydrochloride: Oxycodone Hydrochloride 10 mg tablet</description>
        </group>
        <group group_id="E2">
          <title>Buprenorphine Sublingual Spray 0.5 mg</title>
          <description>Buprenorphine Sublingual Spray 0.5 milligrams (mg) three times a day (TID) for 7 days.&#xD;
Buprenorphine Sublingual Spray: Buprenorphine Sublingual Spray 0.5 mg</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 19.0</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="33" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="47" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director, Clinical Development</name_or_title>
      <organization>Insys Therapeutics, Inc.</organization>
      <phone>4805003105</phone>
      <email>gdecastro@insysrx.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/NCT03254459
org study id: INS005-17-111
nct id: NCT03254459
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the safety and tolerability based on the incidence of adverse
      experiences of buprenorphine sublingual spray (0.5 milligrams [mg] three times daily [TID])
      compared with standard post-operative narcotic therapy in participants with postoperative
      pain. Standard post-operative narcotic therapy is defined as morphine intravenous (IV)
      injection (4 mg TID) followed by oxycodone hydrochloride tablet (10 mg TID).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
time frame: Days 1 to 8
description: An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. A TEAE is an AE with onset that occurs after receiving study drug.
measure: Percentage of Participants Provided Rescue Medication for Nausea
time frame: Days 1 to7
description: Zofran was used at the clinician's discretion as rescue medication for nausea.
measure: Time to First Use of Rescue Medication for Nausea Following Each Dose of the Investigational Product (IP)
time frame: Days 1 to 7
description: Zofran was used at the clinician's discretion as rescue medication for nausea. Time "0" is defined as the time of the administration of study drug.
measure: Total Use of Rescue Medication for Nausea Over 0 to 24 Hours, Over 0 to 48 Hours, Over 0-72 Hours and 0-7 Days
time frame: 0 to 24 hours, 0 to 48 hours, 0 to 72 hours and 0 to 7 days
description: Zofran was used at the clinician's discretion as rescue medication for nausea. The total use of rescue medication was calculated for the following 4 time-frames: 0 to 24 hours, 0 to 48 hours, 0 to 72 hours and 0 to 7 days.
measure: Pulse Oximetry Levels at 90 Minutes,12, 24, 48 and 72 Hours
time frame: 90 Minutes,12, 24, 48 and 72 Hours
description: Pulse oximetry is a non-invasive method to measure a person's oxygen saturation.
measure: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings at 90 Minutes,12, 24, 48 and 72 Hours
time frame: Pre-dose and 90 minutes, 12, 24, 48 and 72 hours after first dose
description: A standard 12-lead ECG will be performed after the participant is in the supine (lying face up) position for 5 minutes.
measure: Number of Participants With Abnormal Oral Cavity Examinations
time frame: Pre-dose and 90 minutes, 12, 24, 48 and 72 hours after first dose on Days 1 to 4 and End of Study Day 8
description: Study staff will perform a sublingual (under the tongue) assessment, noting the color of mucosa and whether inflammation is present.
arm group label: Buprenorphine Sublingual Spray 0.5 mg
arm group type: Experimental
description: Buprenorphine Sublingual Spray 0.5 milligrams (mg) three times a day (TID) for 7 days.
arm group label: Standard of Care Narcotic Therapy
arm group type: Active Comparator
description: Morphine intravenous (IV), 4 mg TID for 24 hours, followed by oxycodone hydrochloride tablet, 10 mg TID for 6 days.
intervention type: Drug
intervention name: Buprenorphine Sublingual Spray
description: 0.5 mg Sublingual Spray
arm group label: Buprenorphine Sublingual Spray 0.5 mg
intervention type: Drug
intervention name: Morphine
description: 4 mg Intravenous Injection
arm group label: Standard of Care Narcotic Therapy
intervention type: Drug
intervention name: Oxycodone Hydrochloride
description: 10 mg tablet
arm group label: Standard of Care Narcotic Therapy
intervention type: Drug
intervention name: Zofran
description: 4 mg oral disintegrating tablet (ODT) or IV injection given at the investigator's discretion for nausea
arm group label: Buprenorphine Sublingual Spray 0.5 mg
arm group label: Standard of Care Narcotic Therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Giovanni DeCastro
role: Study Director
affiliation: INSYS Therapeutics Inc
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pain, Postoperative
mesh term: Morphine
mesh term: Oxycodone
mesh term: Buprenorphine
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 