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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Pain, Low Back Pain

Intervention / Treatment
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* Drug: Buprenorphine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BEMA Buprenorphine<br>buprenorphine buccal soluble film | Drug: Buprenorphine<br>* buccal soluble film; applied to the buccal mucosa twice daily<br>* Other names: buprenorphine HCl buccal film;|
| Placebo Comparator: BEMA Placebo<br>placebo buccal soluble film | Drug: Placebo<br>* buccal soluble film; applied to the buccal mucosa twice daily<br>* Other names: BEMA placebo;|

What is the study measuring?
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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 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 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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buccal soluble film, enriched enrollment, randomized withdrawal