Bupivacaine Effectiveness and Safety in SABER® Trial

Study Overview
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Brief Summary
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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 (side effects) associated with the use of SABER-Bupivacaine and how well it works in reducing pain and opioid-related side effects following various kinds of abdominal surgeries.

Official Title
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Bupivacaine Effectiveness and Safety in SABER Trial (BESST)

Conditions
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Postoperative Pain, Abdominal Surgery

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


Participation Criteria
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Eligibility Criteria
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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 years of age and older scheduled to undergo elective general abdominal surgery Patients must be healthy or have only mild systemic disease BMI < 45 Patients must have ECG wave form within normal limits Female and male patients must agree to use medically acceptable method of contraception throughout the entire trial period and for 1 week after the trial participation is completed Exclusion Criteria: Patients who are pregnant or lactating Patients undergoing emergency surgery (unless full consent is obtained and all screening procedures are completed prior to surgery) Significant concomitant surgical procedure History of multiple prior laparotomy procedures Cancer with known metastases pre-operatively, which are suspected to impact post-operative recovery or pain Planned formation of stoma during surgery or plans to undergo another laparotomy procedure within 30 days post-operatively Pre-operative evidence of sepsis or septic shock Pre-operative evaluation that suggests a surgery may preclude full closure of the incision(s) Patients with current or regular use of systemic steroids, anticonvulsants, antiepileptics, antidepressants, or monoamine oxidase inhibitors, who cannot be withdrawn from these medications Patients with current or regular use of drugs known to significantly prolong the QTc interval Patients with known hypersensitivity to local anesthetic agents of the amide type (e.g. lidocaine, bupivacaine) Patients with known hypersensitivity to morphine Patients with conditions contraindicated for use of opioids Patients with atrial fibrillation/flutter or other non-sinus rhythm (including paced rhythm); left bundle branch block (LBBB); or the following conditions: right bundle branch block (RBBB) in presence of a cardiac disease, significant cardiomyopathy, and myocardial infarction within last 6 months Patients with a serum creatinine level two times more than the local laboratory normal limit Patients who have received greater than 600 mg morphine equivalent daily dose for three or more days per week in the month prior to the surgical procedure Patients who are currently being treated with methadone, or history of methadone use within the previous 6 months 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
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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: Active: SABER-Bupivacaine<br>SABER-Bupivacaine | Drug: SABER-Bupivacaine<br>* Injectable Extended Release Solution; SABER-Bupivacaine /Once<br>* Other names: POSIMIR® bupivacaine solution;|
| Active Comparator: Comparator: Bupivacaine HCl<br>Bupivacaine HCl | Drug: Bupivacaine HCl<br>* Injectable Solution; Bupivacaine HCl /Once<br>|
| Placebo Comparator: Placebo: SABER-Placebo<br>SABER-Placebo | Drug: SABER-Placebo<br>* Injectable Solution; SABER-Placebo/Once<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Pain Intensity on Movement | Mean pain intensity on movement AUC (time-normalized AUC) during the period 0 to 72 hours post-dose. Pain intensity was assessed with a standard 0 to 10 numeric rating scale (NRS), where no pain at all was rated as 0 and the worst pain imaginable was rated as 10. The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude. | 0 to 72 hours post-dose | 
| Supplemental Opioid Use | Total morphine-equivalent dose during 0-72 hours post dose. Median values were presented because data was not normally distributed. | 0-72 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Pain Intensity on Movement | Mean pain intensity on movement AUC (time-normalized AUC) during the period 0 to 48 hours post-dose. Pain intensity was assessed with a standard 0 to 10 numeric rating scale (NRS), where no pain at all was rated as 0 and the worst pain imaginable was rated as 10. The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude. | 0 to 48 hours post-dose | 
| Total Morphine-equivalent Dose | Total morphine-equivalent dose during 0-48 hours post dose. | 0-48 hours post dose | 
| Proportion (Percent) of Patients Who Have Evidence of a Wound Infection | From Surgical Wound Healing and Local Tissue Condition Evaluation | 0 to 14 days post-dose (Visits 3 and 4) | 
| Time-to-first Use of Opioid Rescue Medication |  | 0 to 14 days post-dose (Time from extubation until first opioid use) | 
| Number (Incidence) of Participants With Opioid-related Side Effects | AEs include: nausea, vomiting, constipation, dizziness, somnolence, urinary retention, respiratory depression | 0 to 30 days post-dose | 
| Pain Intensity at Rest AUC During 0-72 Hours Post Dose | Mean pain intensity at rest AUC during the period 0 to 72 hours post-dose. Pain intensity was assessed with a standard 0 to 10 numeric rating scale (NRS), where no pain at all was rated as 0 and the worst pain imaginable was rated as 10. The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude. | 0-72 hours post dose | 
| Mean Pain Intensity at Rest AUC During 0-48 Hours Post Dose | Mean pain intensity at rest AUC during the period 0 to 48 hours post-dose. Pain intensity was assessed with a standard 0 to 10 numeric rating scale (NRS), where no pain at all was rated as 0 and the worst pain imaginable was rated as 10. The AUC is computed for each patient using the standard trapezoidal rule and normalised by dividing by the time interval over which it is computed. This normalisation converts the AUC to the natural pain scale (NRS 0-10) to allow for better translation of the clinical treatment effect magnitude. | 0-48 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative pain, Post-operative pain, Opioid, Laparoscopic surgery, Bupivacaine, Local anesthetic