Study of Buprenorphine HCl Buccal Film in the Treatment of Dental Pain

Study Overview
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Brief Summary
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The purpose of this study is to assess the activity of buprenorphine hydrochloride (HCl) buccal film in the treatment of dental pain.

Official Title
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A Double-Blind, Double-Dummy, Placebo- and Active Controlled Evaluation of the Efficacy, Safety and Tolerability of Buprenorphine HCl Buccal Film in the Treatment of Pain Associated With Third Molar Extraction

Conditions
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Dental Pain

Intervention / Treatment
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* Drug: Oxycodone
* Drug: Buprenorphine
* Drug: Placebo Film
* Drug: Placebo Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: extraction of 2 or more third molars, at least 1 of which must be fully or partially impacted in mandibular bone males or non-pregnant females, aged 18 to 45 years good general health and capable of providing informed consent Exclusion Criteria: history of substance abuse or dependence positive urine toxicology screen or alcohol breath test history of hypersensitivity to or allergy to any study drug donation of blood within prior 30 days use of analgesics, caffeine, sedatives, antidepressants, anticoagulant or antiplatelet agents within 24 hours

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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 |
| --- | --- |
| Active Comparator: Standard Opioid<br>Oxycodone 5-mg oral capsule and 2 buccal placebo films | Drug: Oxycodone<br>* Single-dose of over-encapsulated oral 5-mg oxycodone capsule<br>* Other names: Oxycodone capsule;Drug: Placebo Film<br>* Single-dose of placebo buccal film<br>* Other names: BEMA placebo;|
| Experimental: High Dose buprenorphine HCl buccal film<br>Buprenorphine HCl buccal film 0.5-mg modified formulation 1, buccal placebo film, and oral placebo capsule | Drug: Buprenorphine<br>* Single-dose of buprenorphine HCl buccal film<br>* Other names: Buprenorphine HCl buccal soluble film;Drug: Placebo Film<br>* Single-dose of placebo buccal film<br>* Other names: BEMA placebo;Drug: Placebo Capsule<br>* Single-dose of oral placebo capsule<br>* Other names: Oxycodone placebo;|
| Experimental: Mid Dose buprenorphine HCl buccal film<br>Buprenorphine HCl buccal film 0.5-mg modified formulation 2, buccal placebo film, and oral placebo capsule | Drug: Buprenorphine<br>* Single-dose of buprenorphine HCl buccal film<br>* Other names: Buprenorphine HCl buccal soluble film;Drug: Placebo Film<br>* Single-dose of placebo buccal film<br>* Other names: BEMA placebo;Drug: Placebo Capsule<br>* Single-dose of oral placebo capsule<br>* Other names: Oxycodone placebo;|
| Experimental: Low Dose buprenorphine HCl buccal film<br>Buprenorphine HCl buccal film 0.25-mg modified formulation 2, buccal placebo film, and oral placebo capsule | Drug: Buprenorphine<br>* Single-dose of buprenorphine HCl buccal film<br>* Other names: Buprenorphine HCl buccal soluble film;Drug: Placebo Film<br>* Single-dose of placebo buccal film<br>* Other names: BEMA placebo;Drug: Placebo Capsule<br>* Single-dose of oral placebo capsule<br>* Other names: Oxycodone placebo;|
| Placebo Comparator: Placebo<br>Oral placebo capsule and 2 buccal placebo films | Drug: Placebo Film<br>* Single-dose of placebo buccal film<br>* Other names: BEMA placebo;Drug: Placebo Capsule<br>* Single-dose of oral placebo capsule<br>* Other names: Oxycodone placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Pain Intensity Difference From Baseline to 8 Hours | Time-weighted sum of pain intensity difference from baseline to 8 hours (SPID-8) where total score ranges from -80 (worst) to 80 (best) and a higher value indicates greater pain relief. Pain intensity was recorded using an 11-point numeric rating scale (NRS), where 0=none and 10=worst pain imaginable, in response to What is your pain level at this time? | Baseline, 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Pain Relief Over 8 Hours | Time-weighted sum of total pain relief over 8 hours (TOPAR-8) where total score ranges from 0 (worst) to 32 (best) and higher values indicate greater pain relief. Pain relief (PAR) was recorded using a 5-point categorical rating scale, where 0=none, 1=a little, 2=some, 3=a lot, and 4=complete, in response to How much relief have you had from your starting pain? | 8 hours | 
| Sum of Pain Relief and Intensity Differences Over 8 Hours | Time-weighted sum of PAR and pain intensity difference (PID) over 8 hours (SPRID-8) where total score ranges from -80 (worst) to 112 (best) and higher values indicate greater pain relief. PAR was recorded using a 5-point categorical rating scale, where 0=none, 1=a little, 2=some, 3=a lot, and 4=complete, in response to How much relief have you had from your starting pain? PID determined as the change from baseline pain intensity assessment. Pain intensity was recorded using an 11-point NRS, where 0=none and 10=worst pain imaginable, in response to What is your pain level at this time? | 8 hours | 
| Sum of Pain Relief and Intensity Differences Over 2 Hours | Time-weighted sum of PAR and PID over 2 hours (SPRID-2) where total score ranges from 0 (worst) to 8 (best) and higher values indicate greater pain relief. PAR was recorded using a 5-point categorical rating scale, where 0=none, 1=a little, 2=some, 3=a lot, and 4=complete, in response to How much relief have you had from your starting pain? PID determined as the change from baseline pain intensity assessment. Pain intensity was recorded using an 11-point NRS, where 0=none and 10=worst pain imaginable, in response to What is your pain level at this time? | 2 hours | 
| Peak Pain Intensity Difference | The maximum PID at any time following dosing determined from the change from baseline pain intensity assessment. Pain intensity was recorded using an 11-point NRS, where 0=none and 10=worst pain imaginable, in response to What is your pain level at this time? | 24 hours | 
| Peak Pain Relief | Maximum pain relief (PAR) at any time following dosing, recorded using a 5-point categorical rating scale, where 0=none, 1=a little, 2=some, 3=a lot, and 4=complete, in response to How much relief have you had from your starting pain? | 24 hours | 
| Onset of Analgesia | Time to onset of analgesia defined as median time to perceptible pain relief if confirmed by experiencing meaningful pain relief from time of study drug administration. | 8 hours | 
| Duration of Analgesia | Duration of analgesia was the median time to use of rescue medication; earliest concomitant medication start time for medications identified as rescue medications from time of study drug administration. | 24 hours | 
| Percentage of Participants Reporting a Global Rating of Study Drug as Excellent | Subjects rated the global effectiveness of study drug as poor, fair, good, or excellent, in response to Overall, how would you rate the study medication you received for pain? | 8 hours and 24 hours | 
| Percentage of Participants With Excellent Investigator Global Rating of Study Drug | Investigators rated the global effectiveness of study drug as poor, fair, good, or excellent, in response to Overall, how would you rate the study medication for this subject? | 24 hours | 
| Change From Baseline in Cognitive Assessment Using CNS-VS | Cognition assessed using computer-based CNS Vital Signs® neurocognitive function test (CNS-VS), including symbol digit coding, Stroop test, and shifting attention test to measure cognitive flexibility, executive functioning, processing speed, and reaction time(*). Scores are computed from raw score calculations using the data values of individual subtests. An asterisk denotes that lower score is better, otherwise higher scores are better. | Baseline (screening), 2 hours 15 minutes postdose |