Efficacy and Safety Study of Buprenorphine HCl Buccal Film in Subjects With Low Back Pain

A 12-Week, Placebo Controlled, Double Blind, Randomized Withdrawal Study to Evaluate the Efficacy and Safety of Buprenorphine HCl Buccal Film in Subjects With Moderate to Severe Chronic Low Back Pain

The purpose of this study is to determine whether buprenorphine hydrochloride (HCl) buccal film is effective and safe in the treatment of chronic low back pain (CLBP).

Study Overview

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

Detailed Description

This is an enriched enrollment, randomized withdrawal study with an open label, dose-titration period followed by a randomized, double-blind, placebo-controlled treatment period of 12 weeks. During the double-blind treatment period, this study will evaluate the effectiveness of buprenorphine HCl buccal film versus placebo buccal film in treating CLBP in subjects.

Buprenorphine HCl buccal film is an oral transmucosal form of the opioid analgesic, buprenorphine hydrochloride, intended for application to the buccal mucosa. Buprenorphine is a synthetic opioid that is classified as a partial µ-receptor agonist and a Schedule III controlled substance in the United States.

• Study Type: Interventional
• Enrollment (Actual): 334
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Alabama Orthopaedic Center - Research
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research, Inc.
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
  • California
    • Fresno, California, United States, 93710
      • Neuro-Pain Medical Center
    • La Jolla, California, United States, 92037
      • University of California, San Diego Medical Center, UCSD Center for Pain Medicine
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network, Inc.
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Jupiter, Florida, United States, 33458
      • Health Awareness, Inc.
    • Plantation, Florida, United States, 33317
      • Gold Coast Research, LLC
    • Port Orange, Florida, United States, 32129
      • Accord Clinical Research, LLC
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Taylor Research, LLC
  • Illinois
    • Bloomington, Illinois, United States, 61701
      • Millennium Pain Center
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center, LLC
  • Kansas
    • Leawood, Kansas, United States, 66211
      • International Clinical Research Institute
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • MedVadis Research Corporation
  • Nevada
    • Las Vegas, Nevada, United States, 89144
      • Office of Stephen H. Miller, MD
  • New York
    • New York, New York, United States, 10022
      • Research Across American
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Winston-Salem, North Carolina, United States, 27103
      • The Center for Clinical Research, LLC
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Allegheny Pain Management
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • El Paso, Texas, United States, 79902
      • Southwest Urgent Care Center
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Lifetree Clinical Research
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research

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:

• Male or non-pregnant and non-nursing female aged 18 or older
• History of moderate to severe chronic low back pain for ≥3 months with a pain intensity ≥5 [11 point numerical rating scale] reported at the open-label titration period Day 0/1 visit following a washout period (opioids, nonsteroidal anti-inflammatory drugs [NSAIDs], and muscle relaxants) of approximately 12 to 24 hours
• Currently taking ≤60 mg oral morphine/day or equianalgesic dose of another opioid (including opioid naïve) for 1 week or longer
• Stable health, as determined by the Investigator, on the basis of medical history, physical examination, and screening laboratory results so as to comply with all study procedures
• Female subjects of childbearing potential must be using a recognized effective method of birth control
• Written informed consent obtained at Screening, prior to any procedure being performed

Exclusion Criteria:

• Reflex sympathetic dystrophy or causalgia (complex regional pain syndrome), acute spinal cord compression, cauda equina compression, acute nerve root compression, meningitis, and discitis
• Surgical procedure for back pain within 2 months prior to screening or nerve/plexus block within 4 weeks of screening
• Hypokalemia or clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active myocardial ischemia
• Corrected QT (QTc) interval of >450 milliseconds on the 12-lead electrocardiogram (ECG)
• History of long QT syndrome, or an immediate family member with this condition
• Diagnosis of moderate to severe hepatic impairment.
• History of severe emesis with opioids
• Clinically significant sleep apnea

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BEMA Buprenorphine; buprenorphine buccal soluble film	Drug: Buprenorphine; buccal soluble film; applied to the buccal mucosa twice daily; Other Names: BEMA Buprenorphine; BELBUCA; buprenorphine buccal soluble film; buprenorphine HCl buccal film
Placebo Comparator: BEMA Placebo; placebo buccal soluble film	Drug: Placebo; buccal soluble film; applied to the buccal mucosa twice daily; Other Names: Placebo buccal film; BEMA placebo; Placebo buccal soluble film

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pain Intensity From Baseline to Week 12	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
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 in Pain Intensity Over Time Using NRS Scale	Change in pain intensity = average of daily pain scores from the last 7 days prior to each 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; Day 14, Day 28, Day 42, Day 56, Day 70, and Day 84
Number of Participants With Response to Treatment as Assessed by an NRS Scale	Responses are defined as the relative improvement in pain score at week 12 from baseline, calculated from ratings of average pain intensity over the last 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable).	Week 12
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 due to adverse event in the double-blind treatment phase.	Baseline to treatment failure or end of double-blind treatment phase (up to 12 weeks)
Subject Impression of Change in Pain Intensity From Baseline to Week 12 Using PGIC Scale	Subjects assessed changes in activity, limitations, symptoms, and overall quality of life related to their painful condition since beginning treatment using the Patient Global Impression of Change (PGIC), a balanced 7-point scale from 1 (no change or condition got worse) to 7 (a great deal better and considerable improvement that has made all the difference).	Baseline, Week 12
Change From Baseline to Week 12 in Treatment Satisfaction Using TSQM	The Treatment Satisfaction Questionnaire for Medication (TSQM) is a 14-item instrument used to assess the subject's satisfaction with the ability of the study medication to prevent or treat the condition of chronic low back pain (CLBP) for effectiveness, side effects, convenience, and global satisfaction. Scores range from 0 to 100, where a higher score indicates less dissatisfaction (ie, greater satisfaction).	Baseline, Week 12
Change From Baseline to Week 12 in Subject's Overall Satisfaction With Study Drug	Subjects were asked to rate their overall satisfaction with their study drug on a 5-point scale ranging from 1 (poor) to 5 (excellent).	Baseline, Week 12
Change From Baseline to Week 12 in Investigator's Overall Satisfaction With Study Drug	Investigators rated their overall satisfaction with the study drug administered to a given subject on a 5-point scale ranging from 1 (poor) to 5 (excellent).	Baseline, Week 12
Use of Rescue Medication	Calculated from the use of rescue medication recorded in subject diary as the sum of all rescue medication tablets used in the last 7 days previous to the derived visit, divided by the number of days in this duration where the amount was reported.	Day 7, 14, 28, 42, 56, 70, 84, and 91 within double-blind treatment phase

Collaborators and Investigators

• Sponsor: BioDelivery Sciences International
• Investigators: Study Director: Andrew Finn, PharmD, BioDelivery Sciences International, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: December 7, 2010
• First Submitted That Met QC Criteria: December 7, 2010
• First Posted (Estimate): December 8, 2010

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: randomized withdrawal; buccal soluble film; enriched enrollment
• 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: BUP-301