A Safety and Effectiveness Study of SABER®-Bupivacaine for Pain Following Shoulder Surgery

Study Overview
=================
Brief Summary
-----------------
This is a research study testing SABER-Bupivacaine (an experimental pain-relieving medication). SABER-Bupivacaine is designed to continuously deliver bupivacaine, a common local anesthetic, for a few days in order to treat local post-surgical pain. The purpose of this study is to investigate safety (if there are any side effects) associated with the use of SABER-Bupivacaine and how well it works in reducing pain and opioid-related side effects following shoulder surgery.

Official Title
-----------------
A Double-Blind, Multi-Center, Placebo-Controlled Trial of SABER-Bupivacaine for Post-Operative Pain Control and Opioid Sparing/Opioid-Related Adverse Event Reduction Following Arthroscopic Shoulder Surgery

Conditions
-----------------
Postoperative Pain

Intervention / Treatment
-----------------
* Drug: SABER-Bupivacaine
* Drug: SABER-Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must be able to read and understand the consent form, provide written consent, complete trial-related procedures, and communicate with the trial staff. Males and females, 18 to 65 years of age, scheduled for shoulder surgery. Patients must be healthy or have only mild systemic disease. Patients must have ECG wave form within normal limits Patients must have blood pressure within normal range. Male and female patients must agree to use medically acceptable method of contraception throughout the entire trial period and for 1 week after the trial is completed. Patients must refrain from strenuous activities and avoid changes to prescribed exercise levels throughout the course of the trial. Exclusion Criteria: Patients with previous arthroscopic surgery or open surgery on the study shoulder. Patients with chronic pain conditions requiring continuous use of corticosteroids for greater than 3 months. Patients with fibromyalgia, rheumatoid arthritis, and/or sero-negative inflammatory arthropathies. Patients with a below normal calculated creatinine clearance. Patients who are pregnant or lactating. Patients currently receiving more than 20 mg of hydrocodone daily (or equivalent narcotic dose) on routine basis. Patients, who in the Investigator's opinion, have developed opioid tolerance. Patients with current or regular use of anticonvulsants, antiepileptics, antidepressants, or monoamine oxidase inhibitors at screening. Patients with current or regular use of drugs known to significantly prolong the corrected QT interval Patients with known hypersensitivity to local anesthetic agents of the amide type (e.g., lidocaine, bupivacaine). Patients with known hypersensitivity to opioids. Patients with conditions contraindicated for use of opioids. Patients with known or suspected abuse of opioids or other illicit drugs. Patients with known or suspected alcohol abuse. Participation in another clinical trial at the same time or within 30 days of this trial. Patients who, in the Investigator's opinion, should not participate in the trial or may not be capable of following the trial schedule for any reason.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: SABER-Bupivacaine<br>5.0 mL SABER-Bupivacaine/Once | Drug: SABER-Bupivacaine<br>* Injectable Extended Release Solution; 5.0 mL SABER-Bupivacaine/Once<br>* Other names: POSIMIR® bupivacaine solution;|
| Placebo Comparator: Group 2: SABER-Placebo<br>5.0 mL SABER-Placebo/Once | Drug: SABER-Placebo<br>* Injectable Solution; 5.0 mL SABER-Placebo/Once<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Pain Intensity on Movement AUC (Time Normalized Area Under the Curve) During the Period 0 to 72 Hours Post-dose. | Mean pain intensity on movement AUC (time normalized area under the curve) during the period 0 to 72 hours post-dose. Subjects assessed their pain intensity using an 11-point Pain Intensity Numeric Rating Scale (PI-NRS) with NRS scores ranging from 0 (no pain) to 10 (worst pain possible). The pain intensity AUC on movement was computed for each subject using the standard trapezoidal rule. For the purpose of better clinical interpretability of the pain AUC, a normalized AUC was computed by dividing it using the time-interval length over which it was computed. | 0 to 72 hours post-dose | 
| Supplemental Opioid Use | Mean total morphine-equivalent dose during the period 0 to 72 hours post-dose | 0 to 72 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Frequency of subject-reported opioid-related AEs during 0 to 72 hours (0 to 3 days) post-dose and during the trial: constipation, drowsiness, dizziness, nausea, vomiting, respiratory depression, and urinary retention. | 0 to 72 hours post-dose | 
| Mean Pain Intensity on Movement AUC (Time-normalized AUC) During the Period 0 to 48 Hours Post-dose (0 to 2 Days Post-dose). | Mean pain intensity on movement AUC (time-normalized AUC) during the period 0 to 48 hours post-dose (0 to 2 days post-dose). Subjects assessed their pain intensity using an 11-point Pain Intensity Numeric Rating Scale (PI-NRS) with NRS scores ranging from 0 (no pain) to 10 (worst pain possible). The pain intensity AUC on movement was computed for each subject using the standard trapezoidal rule. For the purpose of better clinical interpretability of the pain AUC, a normalized AUC was computed by dividing it using the time-interval length over which it was computed. | 0 to 48 hours post-dose | 
| Supplemental Opioid Use | Mean total morphine-equivalent dose during the period 0 to 48 hours post-dose (0 to 2 days post-dose) | 0 to 48 hours post-dose | 
| Time-to-first Use of Opioid Supplemental Pain Medication |  | 0 to 14 days post-dose | 
| Severity of Opioid-related Side Effects |  | 0 to 14 days post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Postoperative pain, shoulder surgery, opioid