<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/NCT01660763</url>
  </required_header>
  <id_info>
    <org_study_id>IAP311</org_study_id>
    <nct_id>NCT01660763</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Trial to Evaluate the Sufentanil NanoTab® PCA System/15 mcg (Zalviso™) for Post-Operative Pain in Patients After Knee or Hip Replacement Surgery</brief_title>
  <official_title>P3 - A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of the Sufentanil NanoTab® PCA System/15 mcg (Zalviso™) for the Treatment of Post-Operative Pain in Patients After Knee or Hip Replacement Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AcelRx Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AcelRx Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the efficacy and safety of the Sufentanil NanoTab PCA&#xD;
      System/15 mcg to the Placebo Sufentanil NanoTab PCA System for the management of acute&#xD;
      moderate to severe post-operative pain after total unilateral knee or total unilateral hip&#xD;
      replacement surgery.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">May 2013</completion_date>
  <primary_completion_date type="Actual">April 2013</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time-weighted Summed Pain Intensity Difference (SPID) Over the 48-hour Study Period (SPID48).</measure>
    <time_frame>48 hours</time_frame>
    <description>SPID-48 is the sum of the pain intensity difference (PID) over the 48 hour time period. A pain intensity score of 0 (no pain) to 10 (worse possible pain) is obtained before starting the study and throughout the 48 time period. The pain score at each assessment time is subtracted from the baseline pain score to provide the total sum score or SPID-48. A higher SPID-48 is better and indicates a reduction in pain intensity compared to the baseline score. Range of SPID48 scores were -239 to 417.&#xD;
Time-weighted SPID48 = ∑ [T(i) - T(i-1)] x PID(i), where T(0) = Time 0 (baseline), T(i) is the scheduled or unscheduled assessment time, and PID(i) is the PID score at time i for i=0 to 48 hours</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">419</enrollment>
  <condition>Post Operative Pain</condition>
  <arm_group>
    <arm_group_label>Sufentanil NanoTab PCA System/15 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Sufentanil NanoTab PCA System</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sufentanil NanoTab PCA System/15 mcg</intervention_name>
    <description>15 mcg Sufentanil NanoTab dosed sublingually every 20 minutes as needed for pain for at least 48 hours. Patients may elect to remain in study for up to 72 hours.</description>
    <arm_group_label>Sufentanil NanoTab PCA System/15 mcg</arm_group_label>
    <other_name>sufentanil sublingual microtablet system</other_name>
    <other_name>Zalviso™</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Sufentanil NanoTab PCA System</intervention_name>
    <description>Placebo NanoTab dosed sublingually every 20 minutes as needed for pain for at least 48 hours. Patients may elect to remain in study for up to 72 hours.</description>
    <arm_group_label>Placebo Sufentanil NanoTab PCA System</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients who are 18 years of age or older&#xD;
&#xD;
          -  Patients who are scheduled for an elective cemented or uncemented total unilateral&#xD;
             knee replacement or total unilateral hip replacement, under general or spinal&#xD;
             anesthesia that does not include use of an intrathecal opioid&#xD;
&#xD;
          -  Post-surgical patients who have been admitted to the PACU and are expected to remain&#xD;
             hospitalized and to have acute post-operative pain requiring parenteral opioids for at&#xD;
             least 48 hours after surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have undergone a replacement of the same knee or hip&#xD;
&#xD;
          -  Patients who have taken an opioid for more than 30 consecutive days, at a daily dose&#xD;
             of more than 15 mg of morphine (or equivalent), within the past 3 months prior to&#xD;
             surgery (e.g. more than 3 doses per day of Vicodin®, Norco®, Lortab® with 5 mg&#xD;
             hydrocodone per tablet)&#xD;
&#xD;
          -  Patients with an allergy or hypersensitivity to opioids&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pamela Palmer, M.D., PhD</last_name>
    <role>Study Director</role>
    <affiliation>Chief Medical Officer, AcelRx Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Deidre Stonestreet</name>
      <address>
        <city>Damascus</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Jove M, Griffin DW, Minkowitz HS, Ben-David B, Evashenk MA, Palmer PP. Sufentanil Sublingual Tablet System for the Management of Postoperative Pain after Knee or Hip Arthroplasty: A Randomized, Placebo-controlled Study. Anesthesiology. 2015 Aug;123(2):434-43. doi: 10.1097/ALN.0000000000000746.</citation>
    <PMID>26079801</PMID>
  </reference>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <results_first_submitted>October 24, 2013</results_first_submitted>
  <results_first_submitted_qc>January 30, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 3, 2014</results_first_posted>
  <last_update_submitted>September 30, 2015</last_update_submitted>
  <last_update_submitted_qc>September 30, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 20, 2015</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>Sufentanil</mesh_term>
    <mesh_term>Dsuvia</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment period of 9 months - August 2012 through April 2013</recruitment_details>
      <pre_assignment_details>Patients were excluded per protocol exclusion criteria at Screening as well as post surgery for certain conditions including the following:&#xD;
Patients who were not awake or stable&#xD;
Patients with arterial oxygen saturation that couldn't be maintained at 95% or greater&#xD;
Patients with uncontrollable vomiting</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Sufentanil NanoTab PCA System/15 mcg</title>
          <description>Sufentanil NanoTab PCA System/15 mcg : 15 mcg Sufentanil NanoTab dosed sublingually q 20 minutes as needed for pain for at least 48 hours and up to 72 hours</description>
        </group>
        <group group_id="P2">
          <title>Placebo Sufentanil NanoTab PCA System</title>
          <description>Placebo Sufentanil NanoTab PCA System : Placebo NanoTab dosed sublingually q 20 minutes as needed for pain for at least 48 hours and up to 72 hours</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="315"/>
                <participants group_id="P2" count="104"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="215"/>
                <participants group_id="P2" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="100"/>
                <participants group_id="P2" count="61"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="50"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Patient ready for early discharge</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sufentanil NanoTab PCA System/15 mcg</title>
          <description>Sufentanil NanoTab PCA System/15 mcg : 15 mcg Sufentanil NanoTab dosed sublingually q 20 minutes as needed for pain for at least 48 hours. Patient may elect to remain in study for up to 72 hours</description>
        </group>
        <group group_id="B2">
          <title>Placebo Sufentanil NanoTab PCA System</title>
          <description>Placebo Sufentanil NanoTab PCA System : Placebo NanoTab dosed sublingually q 20 minutes as needed for pain for at least 48 hours. Patient may elect to remain in study for up to 72 hours</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="315"/>
            <count group_id="B2" value="104"/>
            <count group_id="B3" value="419"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="129"/>
                    <measurement group_id="B2" value="50"/>
                    <measurement group_id="B3" value="179"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="186"/>
                    <measurement group_id="B2" value="54"/>
                    <measurement group_id="B3" value="240"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="66.6" spread="10.8"/>
                    <measurement group_id="B2" value="65.0" spread="10.5"/>
                    <measurement group_id="B3" value="66.2" spread="10.7"/>
                  </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="188"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="254"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="127"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="165"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="315"/>
                    <measurement group_id="B2" value="104"/>
                    <measurement group_id="B3" value="419"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Time-weighted Summed Pain Intensity Difference (SPID) Over the 48-hour Study Period (SPID48).</title>
        <description>SPID-48 is the sum of the pain intensity difference (PID) over the 48 hour time period. A pain intensity score of 0 (no pain) to 10 (worse possible pain) is obtained before starting the study and throughout the 48 time period. The pain score at each assessment time is subtracted from the baseline pain score to provide the total sum score or SPID-48. A higher SPID-48 is better and indicates a reduction in pain intensity compared to the baseline score. Range of SPID48 scores were -239 to 417.&#xD;
Time-weighted SPID48 = ∑ [T(i) - T(i-1)] x PID(i), where T(0) = Time 0 (baseline), T(i) is the scheduled or unscheduled assessment time, and PID(i) is the PID score at time i for i=0 to 48 hours</description>
        <time_frame>48 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sufentanil NanoTab PCA System/15 mcg</title>
            <description>Sufentanil NanoTab PCA System/15 mcg : 15 mcg Sufentanil NanoTab dosed sublingually every 20 minutes as needed for pain for up to 48 hours. Patients may elect to remain in study for up to 72 hours.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Sufentanil NanoTab PCA System</title>
            <description>Placebo Sufentanil NanoTab PCA System/15 mcg : Placebo NanoTab dosed sublingually every 20 minutes as needed for pain for up to 48 hours. Patients may elect to remain in study for up to 72 hours.</description>
          </group>
        </group_list>
        <measure>
          <title>Time-weighted Summed Pain Intensity Difference (SPID) Over the 48-hour Study Period (SPID48).</title>
          <description>SPID-48 is the sum of the pain intensity difference (PID) over the 48 hour time period. A pain intensity score of 0 (no pain) to 10 (worse possible pain) is obtained before starting the study and throughout the 48 time period. The pain score at each assessment time is subtracted from the baseline pain score to provide the total sum score or SPID-48. A higher SPID-48 is better and indicates a reduction in pain intensity compared to the baseline score. Range of SPID48 scores were -239 to 417.&#xD;
Time-weighted SPID48 = ∑ [T(i) - T(i-1)] x PID(i), where T(0) = Time 0 (baseline), T(i) is the scheduled or unscheduled assessment time, and PID(i) is the PID score at time i for i=0 to 48 hours</description>
          <units>Units 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="315"/>
                <count group_id="O2" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.24" spread="7.02"/>
                    <measurement group_id="O2" value="-11.35" spread="10.55"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>87.59</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>10.88</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>66.20</ci_lower_limit>
            <ci_upper_limit>108.98</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Sufentanil NanoTab PCA System/15 mcg</title>
          <description>Sufentanil NanoTab PCA System/15 mcg : 15 mcg Sufentanil NanoTab dosed sublingually every 20 minutes as needed for pain for up to 48 hours. Patients may elect to remain in study for up to 72 hours.</description>
        </group>
        <group group_id="E2">
          <title>Placebo Sufentanil NanoTab PCA System</title>
          <description>Placebo Sufentanil NanoTab PCA System/15 mcg : Placebo NanoTab dosed sublingually every 20 minutes as needed for pain for up to 48 hours. Patients may elect to remain in study for up to 72 hours.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (11.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Sinus Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Fecal Infection</sub_title>
                <description>Faecaloma</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Coagulopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Oxygen Saturation Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Epididymitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional State</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Renal Failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Apnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <description>Aspiration Pneumonia</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Pulmonary Embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <default_vocab>MedDRA (11.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="171" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <description>All AEs in this table were assessed by the PI as possibly or probably related to study drug</description>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="110" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Oxygen Saturation Decreased</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Sedation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional State</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="104"/>
              </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="15" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="104"/>
              </event>
              <event>
                <sub_title>Orthostatic Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="315"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Pamela Palmer, MD, PhD</name_or_title>
      <organization>AcelRx Pharmaceuticals, Inc</organization>
      <phone>650-216-3504</phone>
      <email>ppalmer@acelrx.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/NCT01660763
org study id: IAP311
nct id: NCT01660763
lead sponsor: 
has dmc: No
The purpose of this study is to compare the efficacy and safety of the Sufentanil NanoTab PCA
      System/15 mcg to the Placebo Sufentanil NanoTab PCA System for the management of acute
      moderate to severe post-operative pain after total unilateral knee or total unilateral hip
      replacement surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time-weighted Summed Pain Intensity Difference (SPID) Over the 48-hour Study Period (SPID48).
time frame: 48 hours
description: SPID-48 is the sum of the pain intensity difference (PID) over the 48 hour time period. A pain intensity score of 0 (no pain) to 10 (worse possible pain) is obtained before starting the study and throughout the 48 time period. The pain score at each assessment time is subtracted from the baseline pain score to provide the total sum score or SPID-48. A higher SPID-48 is better and indicates a reduction in pain intensity compared to the baseline score. Range of SPID48 scores were -239 to 417.
Time-weighted SPID48 = ∑ [T(i) - T(i-1)] x PID(i), where T(0) = Time 0 (baseline), T(i) is the scheduled or unscheduled assessment time, and PID(i) is the PID score at time i for i=0 to 48 hours
arm group label: Sufentanil NanoTab PCA System/15 mcg
arm group type: Experimental
arm group label: Placebo Sufentanil NanoTab PCA System
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Sufentanil NanoTab PCA System/15 mcg
description: 15 mcg Sufentanil NanoTab dosed sublingually every 20 minutes as needed for pain for at least 48 hours. Patients may elect to remain in study for up to 72 hours.
arm group label: Sufentanil NanoTab PCA System/15 mcg
other name: sufentanil sublingual microtablet system
other name: Zalviso™
intervention type: Drug
intervention name: Placebo Sufentanil NanoTab PCA System
description: Placebo NanoTab dosed sublingually every 20 minutes as needed for pain for at least 48 hours. Patients may elect to remain in study for up to 72 hours.
arm group label: Placebo Sufentanil NanoTab PCA System
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pamela Palmer, M.D., PhD
role: Study Director
affiliation: Chief Medical Officer, AcelRx Pharmaceuticals, Inc.
facility: 
country: United States
citation: Jove M, Griffin DW, Minkowitz HS, Ben-David B, Evashenk MA, Palmer PP. Sufentanil Sublingual Tablet System for the Management of Postoperative Pain after Knee or Hip Arthroplasty: A Randomized, Placebo-controlled Study. Anesthesiology. 2015 Aug;123(2):434-43. doi: 10.1097/ALN.0000000000000746.
PMID: 26079801
responsible party type: Sponsor
mesh term: Pain, Postoperative
mesh term: Sufentanil
mesh term: Dsuvia
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 