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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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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: 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

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: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLBP, Chronic Low Back Pain, Chronic Pain, Back Pain