<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/NCT01675167</url>
  </required_header>
  <id_info>
    <org_study_id>EN3409-307</org_study_id>
    <nct_id>NCT01675167</nct_id>
  </id_info>
  <brief_title>Efficacy Study to Evaluate Buprenorphine HCl Buccal Film in Opioid-Experienced Subjects</brief_title>
  <official_title>Phase 3, Double-Blind, Placebo-Controlled Study to Evaluate the Analgesic Efficacy, Safety, and Tolerability of Buprenorphine HCl Buccal Film in Opioid-Experienced Subjects With Chronic Lower Back Pain Requiring Opioid Analgesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BioDelivery Sciences International</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BioDelivery Sciences International</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to determine if buprenorphine hydrochloride (HCl) buccal film is&#xD;
      effective in treating opioid-experienced subjects, with moderate to severe chronic low back&#xD;
      pain (CLBP), who require continuous around-the-clock (ATC) pain relief for an extended period&#xD;
      of time.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline to Week 12 in Average Daily Pain Intensity Scores</measure>
    <time_frame>Baseline, week 12</time_frame>
    <description>Change in pain intensity = average of daily pain scores from the last 7 days prior to week 12 visit - average of daily pain scores for the last 7 days prior to randomization. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Response to Treatment (Responder) Using NRS Scale</measure>
    <time_frame>Prior to open-label titration to week 12 in double-blind treatment</time_frame>
    <description>Responders are subjects who achieve a relative reduction in pain intensity from the start of open-label titration to week 12 in double-blind treatment. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With Opioid Rescue Medication Use</measure>
    <time_frame>Week 1 to Week 12</time_frame>
    <description>Use of analgesic rescue medication recorded in subject diary</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Optimal Dose of Open-label Study Medication</measure>
    <time_frame>Up to 8 weeks in open-label titration</time_frame>
    <description>Overall time to reach the &quot;optimum&quot; dose of study medication required to progress to double-blind treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Treatment Failure in the Double-blind Treatment Phase (up to 12 Weeks)</measure>
    <time_frame>Baseline to treatment failure or end of double-blind treatment phase (up to 12 weeks)</time_frame>
    <description>Treatment failure is defined as study discontinuation due to lack of efficacy or discontinuation due to adverse events in the double-blind treatment phase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global Impression of Change</measure>
    <time_frame>Week 12</time_frame>
    <description>Subjects assessed their change in activity limitations as they relate to their painful condition since beginning treatment using the Patient Global Impression of Change (PGIC) questionnaire, a 7-point scale ranging from 1 (no change [or condition has got worse]) to 7 (a great deal better, and a considerable improvement that made all the difference)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in Roland Morris Disability Questionnaire</measure>
    <time_frame>Baseline, week 12</time_frame>
    <description>Subjects assess disability due to back pain using the Roland Morris Disability Questionnaire (RMDQ) consisting of 24 statements of disability. The score of the RMDQ is the total number of items checked, ranging from 0 to 24 with higher scores indicating greater disability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in Medical Outcome Score Sleep Subscale</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Medical Outcomes Score (MOS) Sleep Scale uses 12 items to measure 6 dimensions of sleep (sleep disturbance, somnolence, sleep adequacy, snoring, awaken short of breath or headache, and quantity of sleep/optimal sleep) and an overall sleep problems index score. The scores of the dimensions (except quantity of sleep/optimal sleep) and of the sleep problem index range on a 0 to 100 scale, with higher scores reflecting more of the attribute implied by the name (eg, greater sleep disturbance, greater adequacy of sleep).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medical Outcomes Score Sleep Subscale - Quantity of Sleep/Optimal Sleep</measure>
    <time_frame>Week 12</time_frame>
    <description>Medical Outcomes Score (MOS) Sleep scale uses 12 items to measure 6 dimensions of sleep (sleep disturbance, somnolence, sleep adequacy, snoring, awaken short of breath or headache, and quantity of sleep/optimal sleep) and an overall sleep problems index score. The quantity of sleep dimension is the average number of hours of sleep per night reported and optimal sleep is when the number of hours of sleep is ≥7.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">815</enrollment>
  <condition>Low Back Pain</condition>
  <arm_group>
    <arm_group_label>Placebo Buccal Film</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Twice Daily Dosing</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Buprenorphine HCl Buccal Film</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Twice Daily Dosing</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Buprenorphine</intervention_name>
    <description>Buprenorphine HCl Buccal Film at doses ranging from 150-900 mcg twice daily</description>
    <arm_group_label>Buprenorphine HCl Buccal Film</arm_group_label>
    <other_name>BELBUCA</other_name>
    <other_name>Buprenorphine HCl Buccal Film</other_name>
    <other_name>BEMA Buprenorphine</other_name>
    <other_name>EN3409</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching Placebo Buccal Film twice daily</description>
    <arm_group_label>Placebo Buccal Film</arm_group_label>
    <other_name>Placebo Buccal Film</other_name>
    <other_name>BEMA Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of moderate to severe low back pain for ≥6 months&#xD;
&#xD;
          -  Treating CLBP with a stable daily maintenance dose of ATC opioid analgesic medication&#xD;
             equivalent to ≥30 mg and ≤160 mg morphine sulfate equivalents (MSE) per day for ≥4&#xD;
             weeks. (Additional as needed [PRN] analgesic rescue medications permitted on top of&#xD;
             the stable daily maintenance dose of ≥30 mg MSE opioid analgesic, but must be included&#xD;
             in the total daily MSE calculation and in combination with the stable daily&#xD;
             maintenance dose not to exceed 160 mg MSE per day)&#xD;
&#xD;
          -  Stable health, as determine by Principal Investigator&#xD;
&#xD;
          -  Females are practicing abstinence, using a medically acceptable form of contraception,&#xD;
             or post-menopausal, biologically sterile, or surgically sterile for more than 1 year&#xD;
&#xD;
          -  Willing and able to comply with all protocol required visits and assessments&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current cancer related pain or received chemotherapy within 6 months of screening&#xD;
&#xD;
          -  Subjects with history of other chronic painful conditions&#xD;
&#xD;
          -  Reflex sympathetic dystrophy or causalgia, acute spinal cord compression, cauda equina&#xD;
             compression, acute nerve root compression, meningitis, or discitis&#xD;
&#xD;
          -  Allergy or contraindications of any opioid or acetaminophen&#xD;
&#xD;
          -  Surgical procedure for relief of pain within 6 months&#xD;
&#xD;
          -  Hypokalemia or clinically unstable cardiac disease, including: unstable atrial&#xD;
             fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active&#xD;
             myocardial ischemia&#xD;
&#xD;
          -  QT interval corrected using Fridericia's formula (QTcF) of ≥450 milliseconds on the&#xD;
             12-lead electrocardiogram (ECG)&#xD;
&#xD;
          -  History of long QT syndrome or a family member with this condition&#xD;
&#xD;
          -  Moderate to severe hepatic impairment&#xD;
&#xD;
          -  Moderate to severe renal impairment&#xD;
&#xD;
          -  Current or past history of alcohol abuse&#xD;
&#xD;
          -  Positive urine toxicology screen for drug of abuse&#xD;
&#xD;
          -  History or abnormalities on physical exam, vital signs, electrocardiogram, or&#xD;
             laboratory values&#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>Andrew Finn, PharmD</last_name>
    <role>Study Director</role>
    <affiliation>BioDelivery Sciences International, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Parkway Medical Center</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haleyville Clinical Research LLC</name>
      <address>
        <city>Haleyville</city>
        <state>Alabama</state>
        <zip>35565</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Horizon Research Group. Inc / Alabama Orthopedice</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Research Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85023</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Global Research</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Catalina Research Institute, LLC</name>
      <address>
        <city>Chino</city>
        <state>California</state>
        <zip>91710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synergy Clinical Research Center of Escondido</name>
      <address>
        <city>Escondido</city>
        <state>California</state>
        <zip>92025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RX Clinical Research, Inc.</name>
      <address>
        <city>Garden Grove</city>
        <state>California</state>
        <zip>92843</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adam D. Karns, MD</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90036</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stamford Therapeutics Consortium</name>
      <address>
        <city>Stamford</city>
        <state>Connecticut</state>
        <zip>06905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Century Clinic Research</name>
      <address>
        <city>Daytona Beach</city>
        <state>Florida</state>
        <zip>32117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avail Clinical Research, LLC</name>
      <address>
        <city>Deland</city>
        <state>Florida</state>
        <zip>32720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Health Center</name>
      <address>
        <city>Ft. Lauderdale</city>
        <state>Florida</state>
        <zip>33312</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eastern Research, Inc.</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Institute of Medical Research</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32257</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Drug Study Institute</name>
      <address>
        <city>Jupiter</city>
        <state>Florida</state>
        <zip>33458</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Awareness, Inc.</name>
      <address>
        <city>Jupiter</city>
        <state>Florida</state>
        <zip>33458</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FPA Clinical Research</name>
      <address>
        <city>Kissimmee</city>
        <state>Florida</state>
        <zip>34741</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Try Research, Inc.</name>
      <address>
        <city>Maitland</city>
        <state>Florida</state>
        <zip>32751</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NEMA Research, Inc.</name>
      <address>
        <city>Naples</city>
        <state>Florida</state>
        <zip>34108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compass Research, LLC</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peninsula Research, Inc.</name>
      <address>
        <city>Ormond Beach</city>
        <state>Florida</state>
        <zip>32174</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gold Coast Research, LLC</name>
      <address>
        <city>Plantation</city>
        <state>Florida</state>
        <zip>33317</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Progressive Medical Research</name>
      <address>
        <city>Port Orange</city>
        <state>Florida</state>
        <zip>32127</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research of West Florida, Inc.</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Palm Beach Research Center</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33409</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Pain Research Institute, LLC</name>
      <address>
        <city>Winter Park</city>
        <state>Florida</state>
        <zip>32789</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlanta Research Center</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30319</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>River Birch Research Alliance, LLC</name>
      <address>
        <city>Blue Ridge</city>
        <state>Georgia</state>
        <zip>30513</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Drug Studies America</name>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgia Institute for Clinical Research, LLC</name>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taylor Research, LLC</name>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgia Pain &amp; Spine Care &amp; Better Health Clinical Research</name>
      <address>
        <city>Newnan</city>
        <state>Georgia</state>
        <zip>30265</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Investigations Specialists, Inc.</name>
      <address>
        <city>Gurnee</city>
        <state>Illinois</state>
        <zip>60031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MediSphere Medical Research, LLC</name>
      <address>
        <city>Evansville</city>
        <state>Indiana</state>
        <zip>47714</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Integrated Clinical Trial Services, Inc</name>
      <address>
        <city>West Des Moines</city>
        <state>Iowa</state>
        <zip>50265</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>International Clinical Research Institute, Inc.</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Willis-Kinghton Physician Network / River Cities International Pain Specialist</name>
      <address>
        <city>Bossier City</city>
        <state>Louisiana</state>
        <zip>71111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trials Management, LLC</name>
      <address>
        <city>Metairie</city>
        <state>Louisiana</state>
        <zip>70006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Best Clinical Trials, LLC</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>River Cities Clinical Research Center</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MedVadis Research Corp.</name>
      <address>
        <city>Watertown</city>
        <state>Massachusetts</state>
        <zip>02472</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Great Lakes Research Group, Inc.</name>
      <address>
        <city>Bay City</city>
        <state>Michigan</state>
        <zip>48706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Center for Clinical Trials</name>
      <address>
        <city>Biloxi</city>
        <state>Mississippi</state>
        <zip>39531</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Office of Robert Kaplan, DO</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Clinical Research</name>
      <address>
        <city>Berlin</city>
        <state>New Jersey</state>
        <zip>08009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Long Island Gastrointestinal Research Group</name>
      <address>
        <city>Great Neck</city>
        <state>New York</state>
        <zip>11023</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Upstate Clinical Research Associates</name>
      <address>
        <city>Williamsville</city>
        <state>New York</state>
        <zip>14221</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PharmQuest, LLC</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27408</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Center for Clinical Research</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Plains Medical Clinic, LLC</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Inquest Center, Ltd</name>
      <address>
        <city>Beavercreek</city>
        <state>Ohio</state>
        <zip>45432</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Horizons Health Research</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prestige Clinical Research</name>
      <address>
        <city>Franklin</city>
        <state>Ohio</state>
        <zip>45005</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Research Institute</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neuropsychiatric Research Center Research</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brandywine Clinical Research</name>
      <address>
        <city>Downingtown</city>
        <state>Pennsylvania</state>
        <zip>19335</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Altoona Center for Clinical Research</name>
      <address>
        <city>Duncansville</city>
        <state>Pennsylvania</state>
        <zip>16635</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Concepts</name>
      <address>
        <city>Rapid City</city>
        <state>South Dakota</state>
        <zip>57702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FutureSearch Clinical Trials</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>KRK Medical Research</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Future Search Trials of Dallas, LP</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Clinical Research of Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77062</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Network</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Innovative Clinical Trials</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Highland Clinical Research</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>August 27, 2012</study_first_submitted>
  <study_first_submitted_qc>August 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2012</study_first_posted>
  <results_first_submitted>November 4, 2015</results_first_submitted>
  <results_first_submitted_qc>January 4, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 3, 2016</results_first_posted>
  <disposition_first_submitted>March 2, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>June 10, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">July 8, 2015</disposition_first_posted>
  <last_update_submitted>January 12, 2017</last_update_submitted>
  <last_update_submitted_qc>January 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">February 27, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CLBP</keyword>
  <keyword>Chronic Low Back Pain</keyword>
  <keyword>Chronic Pain</keyword>
  <keyword>Back Pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Back Pain</mesh_term>
    <mesh_term>Low Back Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Buprenorphine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Of 1656 subjects screened, 938 subjects entered an analgesic taper phase and 1 subject was eligible to bypass the analgesic taper phase; a total of 815 subjects progressed to the open-label (OL) titration phase. Subjects who completed the open-label titration phase (511) were eligible for randomization in the double-blind (DB) treatment phase.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>OL Buprenorphine HCl Buccal Film</title>
          <description>Buprenorphine hydrochloride (HCl) buccal film, 150, 300, 450, 600, 750, or 900 μg, applied to the buccal mucosa every 12 hours for up to 8 weeks in the open-label titration period</description>
        </group>
        <group group_id="P2">
          <title>DB Buprenorphine HCl Buccal Film</title>
          <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 μg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
        </group>
        <group group_id="P3">
          <title>DB Placebo Film</title>
          <description>Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Open-label Titration Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="815"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="511"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="304"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="81"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="63"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="46"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal due to opioid withdrawal</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="55"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Double-blind Treatment Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0">All subjects completing OL titration in the previous period were randomized to a DB treatment.</participants>
                <participants group_id="P2" count="254">Subjects were randomized to DB treatment after completing OL titration in the previous period.</participants>
                <participants group_id="P3" count="257">Subjects were randomized to DB treatment after completing OL titration in the previous period.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="206"/>
                <participants group_id="P3" count="147"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="48"/>
                <participants group_id="P3" count="110"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="19"/>
                <participants group_id="P3" count="61"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="13"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="11"/>
              </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 group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal due to opioid withdrawal</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Analysis based on Intent-to-Treat (ITT) population; all randomized subjects who received at least 1 dose of double-blind study medication. One (1) subject did not receive double-blind study medication and an additional 19 subjects from 1 site were excluded from the population.</population>
      <group_list>
        <group group_id="B1">
          <title>DB Buprenorphine HCl Buccal Film</title>
          <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 μg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
        </group>
        <group group_id="B2">
          <title>DB Placebo Film</title>
          <description>Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</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="243"/>
            <count group_id="B2" value="248"/>
            <count group_id="B3" value="491"/>
          </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="211"/>
                    <measurement group_id="B2" value="206"/>
                    <measurement group_id="B3" value="417"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53.0" lower_limit="27" upper_limit="78"/>
                    <measurement group_id="B2" value="55.0" lower_limit="23" upper_limit="79"/>
                    <measurement group_id="B3" value="54.0" lower_limit="23" upper_limit="79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</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="130"/>
                    <measurement group_id="B2" value="136"/>
                    <measurement group_id="B3" value="266"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="113"/>
                    <measurement group_id="B2" value="112"/>
                    <measurement group_id="B3" value="225"/>
                  </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="243"/>
                    <measurement group_id="B2" value="248"/>
                    <measurement group_id="B3" value="491"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Week 12 in Average Daily Pain Intensity Scores</title>
        <description>Change in pain intensity = average of daily pain scores from the last 7 days prior to week 12 visit - average of daily pain scores for the last 7 days prior to randomization. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).</description>
        <time_frame>Baseline, week 12</time_frame>
        <population>Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication. One (1) subject did not receive double-blind study medication and an additional 19 subjects from 1 site were excluded from the population.</population>
        <group_list>
          <group group_id="O1">
            <title>DB Buprenorphine HCl Buccal Film</title>
            <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 μg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
          <group group_id="O2">
            <title>DB Placebo Film</title>
            <description>Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in Average Daily Pain Intensity Scores</title>
          <description>Change in pain intensity = average of daily pain scores from the last 7 days prior to week 12 visit - average of daily pain scores for the last 7 days prior to randomization. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).</description>
          <population>Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication. One (1) subject did not receive double-blind study medication and an additional 19 subjects from 1 site were excluded from the population.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="243"/>
                <count group_id="O2" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.88" spread="1.785"/>
                    <measurement group_id="O2" value="1.92" spread="1.867"/>
                  </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;.00001</p_value>
            <p_value_desc>P value was adjusted using weighted z-test (CHW).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.98</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.32</ci_lower_limit>
            <ci_upper_limit>-0.64</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Response to Treatment (Responder) Using NRS Scale</title>
        <description>Responders are subjects who achieve a relative reduction in pain intensity from the start of open-label titration to week 12 in double-blind treatment. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).</description>
        <time_frame>Prior to open-label titration to week 12 in double-blind treatment</time_frame>
        <population>Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication. One (1) subject did not receive double-blind study medication and an additional 19 subjects from 1 site were excluded from the population.</population>
        <group_list>
          <group group_id="O1">
            <title>DB Buprenorphine HCl Buccal Film</title>
            <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 μg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
          <group group_id="O2">
            <title>DB Placebo Film</title>
            <description>Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Response to Treatment (Responder) Using NRS Scale</title>
          <description>Responders are subjects who achieve a relative reduction in pain intensity from the start of open-label titration to week 12 in double-blind treatment. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).</description>
          <population>Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication. One (1) subject did not receive double-blind study medication and an additional 19 subjects from 1 site were excluded from the population.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="243"/>
                <count group_id="O2" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Responders with ≥30% pain reduction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="156"/>
                    <measurement group_id="O2" value="76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responders with ≥50% pain reduction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96"/>
                    <measurement group_id="O2" value="42"/>
                  </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>
            <groups_desc>Responders with ≥30% pain reduction</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <method_desc>Stratified by stratum (dose level)</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Responders with ≥50% pain reduction</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <method_desc>Stratified by Stratum (Dose Level)</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects With Opioid Rescue Medication Use</title>
        <description>Use of analgesic rescue medication recorded in subject diary</description>
        <time_frame>Week 1 to Week 12</time_frame>
        <population>Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication. One (1) subject did not receive double-blind study medication and an additional 19 subjects from 1 site were excluded from the population.</population>
        <group_list>
          <group group_id="O1">
            <title>DB Buprenorphine HCl Buccal Film</title>
            <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 μg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
          <group group_id="O2">
            <title>DB Placebo Film</title>
            <description>Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Opioid Rescue Medication Use</title>
          <description>Use of analgesic rescue medication recorded in subject diary</description>
          <population>Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication. One (1) subject did not receive double-blind study medication and an additional 19 subjects from 1 site were excluded from the population.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="243"/>
                <count group_id="O2" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1 (n=242, 246)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="215"/>
                    <measurement group_id="O2" value="228"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2 (n=234, 204)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="202"/>
                    <measurement group_id="O2" value="185"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3 (n=229, 189)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="197"/>
                    <measurement group_id="O2" value="172"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4 (n=229, 179)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="191"/>
                    <measurement group_id="O2" value="164"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5 (n=222, 162)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="186"/>
                    <measurement group_id="O2" value="147"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6 (n=219, 161)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="185"/>
                    <measurement group_id="O2" value="146"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 7 (n=213, 154)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="178"/>
                    <measurement group_id="O2" value="140"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8 (n=210, 152)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="177"/>
                    <measurement group_id="O2" value="137"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 9 (n=207, 146)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="173"/>
                    <measurement group_id="O2" value="129"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10 (n=205, 145)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="172"/>
                    <measurement group_id="O2" value="130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 11 (n=203, 144)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="172"/>
                    <measurement group_id="O2" value="130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=201, 141)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="166"/>
                    <measurement group_id="O2" value="128"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Optimal Dose of Open-label Study Medication</title>
        <description>Overall time to reach the &quot;optimum&quot; dose of study medication required to progress to double-blind treatment</description>
        <time_frame>Up to 8 weeks in open-label titration</time_frame>
        <population>Analysis based on randomized subjects in the Safety population; all subjects who received at least 1 dose of study medication and were randomized into double-blind treatment</population>
        <group_list>
          <group group_id="O1">
            <title>OL Buprenorphine HCl Buccal Film</title>
            <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 μg, applied to the buccal mucosa every 12 hours for up to 8 weeks in the open-label titration period</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Optimal Dose of Open-label Study Medication</title>
          <description>Overall time to reach the &quot;optimum&quot; dose of study medication required to progress to double-blind treatment</description>
          <population>Analysis based on randomized subjects in the Safety population; all subjects who received at least 1 dose of study medication and were randomized into double-blind treatment</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="511"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.5" spread="11.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Treatment Failure in the Double-blind Treatment Phase (up to 12 Weeks)</title>
        <description>Treatment failure is defined as study discontinuation due to lack of efficacy or discontinuation due to adverse events in the double-blind treatment phase.</description>
        <time_frame>Baseline to treatment failure or end of double-blind treatment phase (up to 12 weeks)</time_frame>
        <population>Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication. One (1) subject did not receive double-blind study medication and an additional 19 subjects from 1 site were excluded from the population.</population>
        <group_list>
          <group group_id="O1">
            <title>DB Buprenorphine HCl Buccal Film</title>
            <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 μg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
          <group group_id="O2">
            <title>DB Placebo Film</title>
            <description>Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Treatment Failure in the Double-blind Treatment Phase (up to 12 Weeks)</title>
          <description>Treatment failure is defined as study discontinuation due to lack of efficacy or discontinuation due to adverse events in the double-blind treatment phase.</description>
          <population>Analysis based on ITT population; all randomized subjects who received at least 1 dose of double-blind study medication. One (1) subject did not receive double-blind study medication and an additional 19 subjects from 1 site were excluded from the population.</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="243"/>
                <count group_id="O2" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.9"/>
                    <measurement group_id="O2" value="29.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Global Impression of Change</title>
        <description>Subjects assessed their change in activity limitations as they relate to their painful condition since beginning treatment using the Patient Global Impression of Change (PGIC) questionnaire, a 7-point scale ranging from 1 (no change [or condition has got worse]) to 7 (a great deal better, and a considerable improvement that made all the difference)</description>
        <time_frame>Week 12</time_frame>
        <population>Analysis based on Patient-Reported Outcomes (PRO) population; randomized subjects who received at least 1 dose of double-blind medication and had at least 1 post-dose assessment on PRO measures. Subjects from 1 site excluded from population (19). Includes only participants with PGIC assessment at week 12 (n=231 buprenorphine and n=230 placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>DB Buprenorphine HCl Buccal Film</title>
            <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 μg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
          <group group_id="O2">
            <title>DB Placebo Film</title>
            <description>Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Global Impression of Change</title>
          <description>Subjects assessed their change in activity limitations as they relate to their painful condition since beginning treatment using the Patient Global Impression of Change (PGIC) questionnaire, a 7-point scale ranging from 1 (no change [or condition has got worse]) to 7 (a great deal better, and a considerable improvement that made all the difference)</description>
          <population>Analysis based on Patient-Reported Outcomes (PRO) population; randomized subjects who received at least 1 dose of double-blind medication and had at least 1 post-dose assessment on PRO measures. Subjects from 1 site excluded from population (19). Includes only participants with PGIC assessment at week 12 (n=231 buprenorphine and n=230 placebo).</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="231"/>
                <count group_id="O2" value="230"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" spread="1.86"/>
                    <measurement group_id="O2" value="3.2" spread="1.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in Roland Morris Disability Questionnaire</title>
        <description>Subjects assess disability due to back pain using the Roland Morris Disability Questionnaire (RMDQ) consisting of 24 statements of disability. The score of the RMDQ is the total number of items checked, ranging from 0 to 24 with higher scores indicating greater disability.</description>
        <time_frame>Baseline, week 12</time_frame>
        <population>Analysis based on PRO population; randomized subjects who received at least 1 dose of double-blind study medication and had at least 1 post-dose assessment on PRO measures. Subjects from 1 site are excluded from the population (19). Includes only participants with RMDQ assessment at week 12 (n=225 buprenorphine and n=231 placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>DB Buprenorphine HCl Buccal Film</title>
            <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 μg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
          <group group_id="O2">
            <title>DB Placebo Film</title>
            <description>Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in Roland Morris Disability Questionnaire</title>
          <description>Subjects assess disability due to back pain using the Roland Morris Disability Questionnaire (RMDQ) consisting of 24 statements of disability. The score of the RMDQ is the total number of items checked, ranging from 0 to 24 with higher scores indicating greater disability.</description>
          <population>Analysis based on PRO population; randomized subjects who received at least 1 dose of double-blind study medication and had at least 1 post-dose assessment on PRO measures. Subjects from 1 site are excluded from the population (19). Includes only participants with RMDQ assessment at week 12 (n=225 buprenorphine and n=231 placebo).</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="225"/>
                <count group_id="O2" value="231"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="5.03"/>
                    <measurement group_id="O2" value="1.6" spread="5.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in Medical Outcome Score Sleep Subscale</title>
        <description>Medical Outcomes Score (MOS) Sleep Scale uses 12 items to measure 6 dimensions of sleep (sleep disturbance, somnolence, sleep adequacy, snoring, awaken short of breath or headache, and quantity of sleep/optimal sleep) and an overall sleep problems index score. The scores of the dimensions (except quantity of sleep/optimal sleep) and of the sleep problem index range on a 0 to 100 scale, with higher scores reflecting more of the attribute implied by the name (eg, greater sleep disturbance, greater adequacy of sleep).</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>Analysis based on PRO population; randomized subjects who received at least 1 dose of double-blind study medication and had at least 1 post-dose assessment on PRO measures. Subjects from 1 site are excluded from the population (19). Includes only participants with MOS assessment at week 12 (n=231 buprenorphine and n=230 placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>DB Buprenorphine HCl Buccal Film</title>
            <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 μg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
          <group group_id="O2">
            <title>DB Placebo Film</title>
            <description>Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in Medical Outcome Score Sleep Subscale</title>
          <description>Medical Outcomes Score (MOS) Sleep Scale uses 12 items to measure 6 dimensions of sleep (sleep disturbance, somnolence, sleep adequacy, snoring, awaken short of breath or headache, and quantity of sleep/optimal sleep) and an overall sleep problems index score. The scores of the dimensions (except quantity of sleep/optimal sleep) and of the sleep problem index range on a 0 to 100 scale, with higher scores reflecting more of the attribute implied by the name (eg, greater sleep disturbance, greater adequacy of sleep).</description>
          <population>Analysis based on PRO population; randomized subjects who received at least 1 dose of double-blind study medication and had at least 1 post-dose assessment on PRO measures. Subjects from 1 site are excluded from the population (19). Includes only participants with MOS assessment at week 12 (n=231 buprenorphine and n=230 placebo).</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="231"/>
                <count group_id="O2" value="230"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Sleep problems index</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.36" spread="7.857"/>
                    <measurement group_id="O2" value="-1.37" spread="8.359"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep disturbance</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.93" spread="10.739"/>
                    <measurement group_id="O2" value="-3.54" spread="12.038"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Somnolence</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.20" spread="12.927"/>
                    <measurement group_id="O2" value="-0.38" spread="15.301"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep adequacy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.13" spread="17.924"/>
                    <measurement group_id="O2" value="3.61" spread="18.326"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Snoring</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.87" spread="18.630"/>
                    <measurement group_id="O2" value="-2.78" spread="15.945"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Awaken short of breath or headache</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.52" spread="17.288"/>
                    <measurement group_id="O2" value="-4.26" spread="19.628"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Medical Outcomes Score Sleep Subscale - Quantity of Sleep/Optimal Sleep</title>
        <description>Medical Outcomes Score (MOS) Sleep scale uses 12 items to measure 6 dimensions of sleep (sleep disturbance, somnolence, sleep adequacy, snoring, awaken short of breath or headache, and quantity of sleep/optimal sleep) and an overall sleep problems index score. The quantity of sleep dimension is the average number of hours of sleep per night reported and optimal sleep is when the number of hours of sleep is ≥7.</description>
        <time_frame>Week 12</time_frame>
        <population>Analysis based on PRO population; randomized subjects who received at least 1 dose of double-blind study medication and had at least 1 post-dose assessment on PRO measures. Subjects from 1 site are excluded from the population (19). Includes only participants with MOS assessment at week 12 (n=231 buprenorphine and n=230 placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>DB Buprenorphine HCl Buccal Film</title>
            <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 μg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
          <group group_id="O2">
            <title>DB Placebo Film</title>
            <description>Placebo buccal film applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind treatment period</description>
          </group>
        </group_list>
        <measure>
          <title>Medical Outcomes Score Sleep Subscale - Quantity of Sleep/Optimal Sleep</title>
          <description>Medical Outcomes Score (MOS) Sleep scale uses 12 items to measure 6 dimensions of sleep (sleep disturbance, somnolence, sleep adequacy, snoring, awaken short of breath or headache, and quantity of sleep/optimal sleep) and an overall sleep problems index score. The quantity of sleep dimension is the average number of hours of sleep per night reported and optimal sleep is when the number of hours of sleep is ≥7.</description>
          <population>Analysis based on PRO population; randomized subjects who received at least 1 dose of double-blind study medication and had at least 1 post-dose assessment on PRO measures. Subjects from 1 site are excluded from the population (19). Includes only participants with MOS assessment at week 12 (n=231 buprenorphine and n=230 placebo).</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="231"/>
                <count group_id="O2" value="230"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Quantity of Sleep/Optimal Sleep ≥7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75"/>
                    <measurement group_id="O2" value="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Quantity of Sleep/Optimal Sleep &lt;7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="156"/>
                    <measurement group_id="O2" value="149"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From informed consent at screening through 14 days after last dose in the double-blind treatment phase (up to 26 weeks)</time_frame>
      <desc>Analysis based on Safety population; all enrolled subjects who received at least 1 dose of study drug in the respective period (open-label titration and double-blind treatment)</desc>
      <group_list>
        <group group_id="E1">
          <title>OL Buprenorphine HCl Buccal Film</title>
          <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 µg, applied to the buccal mucosa every 12 hours for up to 8 weeks in the open-label titration period</description>
        </group>
        <group group_id="E2">
          <title>DB Buprenorphine HCl Buccal Film</title>
          <description>Buprenorphine HCl buccal film, 150, 300, 450, 600, 750, or 900 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind titration period</description>
        </group>
        <group group_id="E3">
          <title>DB Placebo Film</title>
          <description>Placebo buccal film, 150, 300, 450, 600, 750, or 900 µg, applied to the buccal mucosa every 12 hours for 12 weeks in the double-blind titration period</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 16.0</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="14" subjects_at_risk="810"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="254"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Pancreatitis relapsing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Impaired healing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="810"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abscess limb</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="254"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Kidney infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Pneumonia staphylococcal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Pulmonary contusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="810"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="810"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Venous insufficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 16.0</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="268" subjects_at_risk="810"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="254"/>
                <counts group_id="E3" subjects_affected="49" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="73" subjects_affected="67" subjects_at_risk="810"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="254"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="167" subjects_affected="136" subjects_at_risk="810"/>
                <counts group_id="E2" events="19" subjects_affected="19" subjects_at_risk="254"/>
                <counts group_id="E3" events="19" subjects_affected="19" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="63" subjects_affected="54" subjects_at_risk="810"/>
                <counts group_id="E2" events="15" subjects_affected="14" subjects_at_risk="254"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Drug withdrawal syndrome</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="810"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="254"/>
                <counts group_id="E3" events="25" subjects_affected="25" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="47" subjects_affected="42" subjects_at_risk="810"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="254"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="61" subjects_affected="54" subjects_at_risk="810"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="254"/>
                <counts group_id="E3" events="8" subjects_affected="8" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="54" subjects_affected="41" subjects_at_risk="810"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="256"/>
              </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>PI and Institution reserve the right to publish and present the results of the work performed provided that Institution and/or PI submits a copy of any proposed publication to Sponsor's agent for review and comment at least 90 days in advance of its presentation or submission for publication. In addition, if Sponsor's agent requests, Institution and/or PI will withhold publication or presentation for an additional 60 days to allow for establishing and preserving its proprietary rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Trial Coordinator</name_or_title>
      <organization>Endo Pharmaceuticals Inc.</organization>
      <email>clinicalsite.inquiries@endo.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/NCT01675167
org study id: EN3409-307
nct id: NCT01675167
lead sponsor: 
has dmc: No
The purpose of the study is to determine if buprenorphine hydrochloride (HCl) buccal film is
      effective in treating opioid-experienced subjects, with moderate to severe chronic low back
      pain (CLBP), who require continuous around-the-clock (ATC) pain relief for an extended period
      of time.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline to Week 12 in Average Daily Pain Intensity Scores
time frame: Baseline, week 12
description: Change in pain intensity = average of daily pain scores from the last 7 days prior to week 12 visit - average of daily pain scores for the last 7 days prior to randomization. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).
measure: Number of Participants With Response to Treatment (Responder) Using NRS Scale
time frame: Prior to open-label titration to week 12 in double-blind treatment
description: Responders are subjects who achieve a relative reduction in pain intensity from the start of open-label titration to week 12 in double-blind treatment. Average pain intensity over the last 24 hours was rated on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).
measure: Number of Subjects With Opioid Rescue Medication Use
time frame: Week 1 to Week 12
description: Use of analgesic rescue medication recorded in subject diary
measure: Time to Optimal Dose of Open-label Study Medication
time frame: Up to 8 weeks in open-label titration
description: Overall time to reach the "optimum" dose of study medication required to progress to double-blind treatment
measure: Percentage of Participants With Treatment Failure in the Double-blind Treatment Phase (up to 12 Weeks)
time frame: Baseline to treatment failure or end of double-blind treatment phase (up to 12 weeks)
description: Treatment failure is defined as study discontinuation due to lack of efficacy or discontinuation due to adverse events in the double-blind treatment phase.
measure: Patient Global Impression of Change
time frame: Week 12
description: Subjects assessed their change in activity limitations as they relate to their painful condition since beginning treatment using the Patient Global Impression of Change (PGIC) questionnaire, a 7-point scale ranging from 1 (no change [or condition has got worse]) to 7 (a great deal better, and a considerable improvement that made all the difference)
measure: Change From Baseline to Week 12 in Roland Morris Disability Questionnaire
time frame: Baseline, week 12
description: Subjects assess disability due to back pain using the Roland Morris Disability Questionnaire (RMDQ) consisting of 24 statements of disability. The score of the RMDQ is the total number of items checked, ranging from 0 to 24 with higher scores indicating greater disability.
measure: Change From Baseline to Week 12 in Medical Outcome Score Sleep Subscale
time frame: Baseline, Week 12
description: Medical Outcomes Score (MOS) Sleep Scale uses 12 items to measure 6 dimensions of sleep (sleep disturbance, somnolence, sleep adequacy, snoring, awaken short of breath or headache, and quantity of sleep/optimal sleep) and an overall sleep problems index score. The scores of the dimensions (except quantity of sleep/optimal sleep) and of the sleep problem index range on a 0 to 100 scale, with higher scores reflecting more of the attribute implied by the name (eg, greater sleep disturbance, greater adequacy of sleep).
measure: Medical Outcomes Score Sleep Subscale - Quantity of Sleep/Optimal Sleep
time frame: Week 12
description: Medical Outcomes Score (MOS) Sleep scale uses 12 items to measure 6 dimensions of sleep (sleep disturbance, somnolence, sleep adequacy, snoring, awaken short of breath or headache, and quantity of sleep/optimal sleep) and an overall sleep problems index score. The quantity of sleep dimension is the average number of hours of sleep per night reported and optimal sleep is when the number of hours of sleep is ≥7.
arm group label: Placebo Buccal Film
arm group type: Placebo Comparator
description: Twice Daily Dosing
arm group label: Buprenorphine HCl Buccal Film
arm group type: Experimental
description: Twice Daily Dosing
intervention type: Drug
intervention name: Buprenorphine
description: Buprenorphine HCl Buccal Film at doses ranging from 150-900 mcg twice daily
arm group label: Buprenorphine HCl Buccal Film
other name: BELBUCA
other name: Buprenorphine HCl Buccal Film
other name: BEMA Buprenorphine
other name: EN3409
intervention type: Drug
intervention name: Placebo
description: Matching Placebo Buccal Film twice daily
arm group label: Placebo Buccal Film
other name: Placebo Buccal Film
other name: BEMA Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew Finn, PharmD
role: Study Director
affiliation: BioDelivery Sciences International, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Back Pain
mesh term: Low Back Pain
mesh term: Buprenorphine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 