Buprenorphine Sublingual Spray for the Treatment of Moderate to Severe Pain

Study Overview
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Brief Summary
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This is a phase 3, multicenter, randomized, double-blind, multiple-dose, parallel-group, placebo-controlled study to evaluate the safety and efficacy of up to 3 dosing regimens of Buprenorphine Sublingual (under the tongue) Spray and/or matching placebo in participants with moderate to severe postoperative pain after bunionectomy. The study will comprise 4 periods: the Screening Period, the Surgical Period, the Treatment Period, and the Follow-up Period. Participants will be admitted to the study site on the morning of the scheduled surgery, will remain at the study site until postoperative Day 3 (a total of 3 nights at the study site), and will return for the Follow-up Visit 5 to 9 days after surgery.

Official Title
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A Phase 3, Randomized, Double-Blind, Multiple-Dose, Parallel-Group, Placebo-Controlled Study of Buprenorphine Sublingual Spray for the Treatment of Moderate to Severe Pain

Conditions
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Post-operative Pain

Intervention / Treatment
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* Drug: Buprenorphine Sublingual Spray
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets protocol-specified criteria for qualification and contraception Is able to speak and understand the language in which the study is being conducted, is able to understand the procedures and study requirements and has voluntarily signed and dated an informed consent form approved by the Institutional Review Board before the conduct of any study procedure Is willing and able to comply with study requirements (including diet, alcohol, and smoking restrictions), complete the pain evaluations, remain at the study site for three days, and return for follow up between 7 and 9 days after surgery. Exclusion Criteria: History or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters Signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise: the safety or well-being of the participant or study staff the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding) the analysis of results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Experimental: Buprenorphine 0.5 mg TID<br>Participants received buprenorphine 0.5 mg sublingual spray three times daily (TID) and placebo-matching buprenorphine sublingual spray once daily (QD) for two days. | Drug: Buprenorphine Sublingual Spray<br>* Buprenorphine sublingual spray delivered via single 100 μL spray<br>Drug: Placebo<br>* Placebo-matching buprenorphine sublingual spray delivered via single 100 μL spray<br>|
| Experimental: Buprenorphine 1.0 mg BID<br>Participants received buprenorphine 1.0 mg sublingual spray twice daily (BID) and placebo-matching buprenorphine sublingual spray BID for two days. | Drug: Buprenorphine Sublingual Spray<br>* Buprenorphine sublingual spray delivered via single 100 μL spray<br>Drug: Placebo<br>* Placebo-matching buprenorphine sublingual spray delivered via single 100 μL spray<br>|
| Experimental: Buprenorphine 1.0 mg TID<br>Participants received buprenorphine 1.0 mg sublingual spray TID and placebo-matching buprenorphine sublingual spray QD for two days. | Drug: Buprenorphine Sublingual Spray<br>* Buprenorphine sublingual spray delivered via single 100 μL spray<br>Drug: Placebo<br>* Placebo-matching buprenorphine sublingual spray delivered via single 100 μL spray<br>|
| Placebo Comparator: Placebo<br>Participants received placebo-matching buprenorphine sublingual spray four times daily for two days. | Drug: Placebo<br>* Placebo-matching buprenorphine sublingual spray delivered via single 100 μL spray<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Rating Scale (NRS) Summed Pain Intensity Difference (SPID) Over 0 to 48 Hours After Time 0 (NRS SPID-48) | Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 48 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain [maximum (max)=10 at each time point] and negative numbers indicate an increase in pain [minimum (min)=-10 at each time point]. The overall min and max are -10 and 10 times the number of hours specified; SPID-48 range is -480 to 480. The NRS SPID-48 was analyzed using an analysis of covariance (ANCOVA) model, which included treatment and site as main effects and Baseline pain intensity as the covariate. | Baseline and 0 to 48 hours after Time 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NRS Mean Pain Intensity Difference (PID) at 4, 8, 24 and 48 Hours After Time 0 | Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug administration) and at multiple time points up to 48 hours after Time 0 (time of administration of the first dose of study drug). NRS PID is defined as the difference in pain at each scheduled timepoint relative to Baseline (PID=pain intensity at baseline - pain intensity at time point). A higher value of NRS PID score indicates a higher decrease in pain from Baseline. | Baseline and 4, 8, 24 and 48 hours after Time 0 | 
| NRS Mean Pain Intensity Score at 4, 8, 24 and 48 Hours After Time 0 | Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug administration) and at multiple time points up to 48 hours after Time 0 (time of administration of the first dose of study drug). A lower value indicates improvement in pain. | 4, 8, 24 and 48 hours after Time 0 | 
| NRS SPID Over 0 to 4 Hours After Time 0 (NRS SPID-4) | Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 4 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain [maximum (max)=10 at each time point] and negative numbers indicate an increase in pain [minimum (min)=-10 at each time point]. The overall min and max are -10 and 10 times the number of hours specified; SPID-4 range is -40 to 40. The NRS SPID-4 was analyzed using an analysis of covariance (ANCOVA) model, which included treatment and site as main effects and Baseline pain intensity as the covariate. | Baseline and 0 to 4 hours after Time 0 | 
| NRS SPID Over 0 to 8 Hours After Time 0 (NRS SPID-8) | Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 8 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain [maximum (max)=10 at each time point] and negative numbers indicate an increase in pain [minimum (min)=-10 at each time point]. The overall min and max are -10 and 10 times the number of hours specified; SPID-8 range is -80 to 80. The NRS SPID-8 was analyzed using an analysis of covariance (ANCOVA) model, which included treatment and site as main effects and Baseline pain intensity as the covariate. | Baseline and 0 to 8 hours after Time 0 | 
| NRS SPID Over 0 to 24 Hours After Time 0 (NRS SPID-24) | Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 24 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain [maximum (max)=10 at each time point] and negative numbers indicate an increase in pain [minimum (min)=-10 at each time point]. The overall min and max are -10 and 10 times the number of hours specified; SPID-24 range is -240 to 240. The NRS SPID-24 was analyzed using an analysis of covariance (ANCOVA) model, which included treatment and site as main effects and Baseline pain intensity as the covariate. | Baseline and 0 to 24 hours after Time 0 | 
| Percentage of Participants Who Used Rescue Medication for Pain | The percentage of participants who needed to take an alternate medication for pain relief during the study. | From Time 0 (first dose of study drug) up to Day 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bunionectomy