Efficacy Study to Evaluate Buprenorphine HCl Buccal Film in Opioid-Naive Subjects

Phase 3, Double-Blind, Placebo-Controlled, Study to Evaluate the Analgesic Efficacy, Safety, and Tolerability of Buprenorphine HCl Buccal Film in Opioid-Naive Subjects With Chronic Lower Back Pain Requiring Opioid Analgesia

The purpose of this study is to determine if buprenorphine hydrochloride (HCl) buccal film is effective in treating opioid-naive 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.

Study Overview

• Status: Completed
• Conditions: Low Back Pain
• Intervention / Treatment: Drug: Placebo; Drug: Buprenorphine

• Study Type: Interventional
• Enrollment (Actual): 752
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Horizon Research Group, Inc./Alabama Orthopedic Clinic
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
  • California
    • Anaheim, California, United States, 92804
      • Global Research
    • Chino, California, United States, 91710
      • Catalina Research Institute, LLC
    • Escondido, California, United States, 92025
      • Synergy Clinical Research Center Of Escondido
    • Los Angeles, California, United States, 90036
      • Adam D. Karns MD
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Stamford Therapeutics Consortium
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida - Clearwater
    • Daytona Beach, Florida, United States, 32117
      • Century Clinical Research, Inc.
    • Deland, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Ft. Lauderdale, Florida, United States, 33312
      • Florida Health Center
    • Hialeah, Florida, United States, 33013
      • Eastern Research, Inc.
    • Jacksonville, Florida, United States, 32257
      • Florida Institute of Medical Research
    • Jupiter, Florida, United States, 33458
      • Health Awareness, Inc.
    • Jupiter, Florida, United States, 33458
      • Drug Study Institute
    • Naples, Florida, United States, 34108
      • NEMA Research, Inc.
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Ormond Beach, Florida, United States, 32174
      • Peninsula Research
    • Plantation, Florida, United States, 33317
      • Gold Coast Research, L.L.C.
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida - Tampa
    • Winter Park, Florida, United States, 32789
      • National Pain Research Institute, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30319
      • Atlanta Research Center
    • Blue Ridge, Georgia, United States, 30513
      • River Birch Research Alliance, LLC
    • Marietta, Georgia, United States, 30060
      • Georgia Institute for Clinical Research, LLC
    • Marietta, Georgia, United States, 30060
      • Taylor Research, LLC
    • Marietta, Georgia, United States, 30060
      • Drug Studies America
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center, LLC
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Integrated Clinical Trial Services, Inc.
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • International Clinical Research Institute, Inc.
  • Louisiana
    • Bossier City, Louisiana, United States, 71111
      • Willis-Kinghton Physician Network/River Interventional Pain Specialist
    • Metairie, Louisiana, United States, 70006
      • Clinical Trials Management, LLC
    • New Orleans, Louisiana, United States, 70115
      • Best Clinical Trials, Inc.
    • Shreveport, Louisiana, United States, 71105
      • River Cities Clinical Research Center
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • MedVadis Research Corp.
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Great Lakes Research Group, Inc.
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • The Center for Clinical Trials
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Office of Robert Kaplan, DO
  • New York
    • Great Neck, New York, United States, 11023
      • Long Island Gastrointestinal Research Group
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates LLC
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest, LLC
    • Winston Salem, North Carolina, United States, 27103
      • The Center for Clinical Research
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Plains Medical Clinic, LLC
  • Ohio
    • Beavercreek, Ohio, United States, 45432
      • Clinical Inquest Center, Ltd.
    • Cincinnati, Ohio, United States, 45242
      • New Horizons Clinical Research
    • Columbus, Ohio, United States, 43235
      • Optimed Research, Ltd.
    • Franklin, Ohio, United States, 45005
      • Prestige Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Health Research Institute
    • Oklahoma City, Oklahoma, United States, 73109
      • NPC Research
  • Pennsylvania
    • Downingtown, Pennsylvania, United States, 19335
      • Brandywine Clinical Research
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Clinical Trials - Austin
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Dallas, Texas, United States, 75230
      • KRK Medical Research
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77062
      • Advanced Clinical Research of Houston
    • San Antonio, Texas, United States, 78229
      • Innovative Clinical Trials
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Highland Clinical Research
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53142
      • Clinical Investigations Specialists, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of moderate to severe low back pain for ≥6 months
• Treating CLBP with a stable daily maintenance dose of non-opioid analgesic medication up to 10 mg morphine sulfate equivalents (MSE) per day for ≥4 weeks. (Additional as needed [PRN] non-opioid analgesic medications permitted on top of the stable daily maintenance dose of non-opioid analgesic)
• Stable health, as determined by Principal Investigator
• Are female who are practicing abstinence or using a medically acceptable form of contraception or have been post-menopausal, biologically sterile, or surgically sterile for more than 1 year
• Willing and able to comply with all protocol required visits and assessments

Exclusion Criteria:

• Current cancer related pain or received chemotherapy with 6 months of screening
• Receiving opioid analgesic medication >10 mg MSE per day within 28 days of screening
• Subjects with a history of other chronic painful conditions
• Reflex sympathetic dystrophy or causalgia, acute spinal cord compression, cauda equina compression, acute nerve root compression, meningitis, or discitis
• Allergy or contraindications to any opioid or acetaminophen
• Surgical procedure for relief of pain with 6 months
• Hypokalemia or clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active myocardial ischemia
• QT interval corrected using Fridericia's formula (QTcF) of ≥450 milliseconds on the 12-lead electrocardiogram (ECG)
• History of long QT syndrome or a family member with this condition
• Moderate to severe hepatic impairment
• Moderate to severe renal impairment
• Current or past history of alcohol abuse
• Positive urine toxicology screen for drug of abuse
• History or abnormalities on physical exam, vital signs, electrocardiogram, or laboratory values

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Twice Daily Dosing	Drug: Placebo; Matching Placebo Buccal Film twice daily; Other Names: Placebo Buccal Film; BEMA Placebo
Experimental: Buprenorphine HCl Buccal Film; Twice Daily Dosing	Drug: Buprenorphine; Buprenorphine HCl Buccal Film at doses ranging from 75-600 mcg twice daily; Other Names: BEMA Buprenorphine; BELBUCA; EN3409; Buprenorphine HCl Buccal Film

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 in Average Daily Pain Intensity Scores	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).	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Response to Treatment (Responder) Using NRS Scale	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 NRS ranging from 0 (no pain) to 10 (worst pain imaginable).	Prior to open-label titration to Week 12 in double-blind treatment
Number of Subjects With Rescue Medication Use	Use of analgesic rescue medication recorded in subject diary.	Week 1 to Week 12 in double-blind treatment
Time to Optimal Dose of Open-label Study Medication	Overall time to reach the "optimal" dose of study medication required to progress to double-blind treatment.	Up to 8 weeks in open-label titration
Percentage of Participants With Treatment Failure in the Double-blind Treatment Phase (up to 12 Weeks)	Treatment failure is defined as study discontinuation due to lack of efficacy or discontinuation due to adverse events in the double-blind treatment phase.	Baseline to treatment failure or end of double-blind treatment phase (up to 12 weeks)
Patient Global Impression of Change	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)	Week 12
Change From Baseline to Week 12 in Roland Morris Disability Questionnaire	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.	Baseline, Week 12
Change From Baseline to Week 12 in Medical Outcomes Score Sleep Subscale	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).	Baseline, Week 12

Collaborators and Investigators

• Sponsor: BioDelivery Sciences International
• Investigators: Study Director: M. Todd Kirby, PhD, Endo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: July 2, 2012
• First Submitted That Met QC Criteria: July 5, 2012
• First Posted (Estimate): July 6, 2012

Study Record Updates

• Last Update Posted (Actual): February 27, 2017
• Last Update Submitted That Met QC Criteria: January 12, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Chronic Pain; Chronic Low Back Pain; Back Pain; CLBP
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: EN3409-308