A Safety and Efficacy Study of SABER®-Bupivacaine for Pain Following Hernia Repair

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. This study is testing SABER-Bupivacaine in people having surgery to repair a hernia. The purpose of the study is to measure and compare the safety (side effects), tolerability (ability to tolerate), and efficacy (how well it works) of two different volumes of SABER-Bupivacaine with SABER-Placebo.

Official Title
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A Double-Blind, Placebo-Controlled, Pharmacodynamic and Pharmacokinetic Dose Response Study of SABER-Bupivacaine Instilled Into the Wound in Patients Undergoing Open Inguinal Hernia Repair

Conditions
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Postoperative Pain, Hernia, Surgery

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, 18 to 65 years of age, scheduled for hernia repair surgery Patients must be in good health prior to study participation Patients must have blood pressure within normal range or with Stage 1 high blood pressure 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 Ability to read, understand, communicate, and voluntarily sign the informed consent form prior to any trial specific procedures Exclusion Criteria: Patients with previous abdominal surgery scar tissue Patients with clinically significant abnormalities of any body system unrelated to the disease under study Connective tissue disorders Patients who are pregnant or lactating Current or regular use of analgesic medication for other indications Patients with current or regular use of antidepressants or monoamine oxidase inhibitors at screening Use of any drugs or medication that may interfere with the study and its results Patients with known hypersensitivity to the study drugs or their components Patients with known or suspected alcohol abuse or illicit drug use Participation in another clinical trial at the same time or within 30 days of this trial Patient is unwilling to comply with the study procedures

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: SABER-Bupivacaine<br>2.5 mL SABER-Bupivacaine/Once | Drug: SABER-Bupivacaine<br>* Injectable Extended Release Solution; 2.5 mL SABER-Bupivacaine/Once<br>|
| Experimental: Group 2: 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 3: SABER-Placebo<br>2.5 mL or 5.0 mL SABER-Placebo/Once | Drug: SABER-Placebo<br>* Injectable Solution; 2.5 or 5.0 mL SABER-Placebo/Once<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity on Movement | Pain intensity on movement normalized AUC over the time period 1 to 72 hours post-surgery. Data on pain intensity were collected using a 0 to 10 NRS with scores ranging from 0 (no pain) to 10 (worst pain possible). 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. | 1 to 72 hours post-dose | 
| Proportion (Percent) of Patients Using Supplemental Opioids |  | 0 to 14 days post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity | Pain intensity AUC over the time period of 1 to 48 hours. Data on pain intensity were collected using a 0 to 10 NRS with scores ranging from 0 (no pain) to 10 (worst pain possible). 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. | 1 to 48 hours post-dose | 
| Treatment Satisfaction | Modified Brief Pain Inventory -An overall assessment of treatment satisfaction was made using 6 point verbal rating scale (very dissatisfied, dissatisfied, slightly dissatisfied, slightly satisfied, satisfied, very satisfied). | 1 to 5 days post-dose | 
| Supplemental Opioid Use |  | 0 to 14 days post-dose | 
| Mean Function Activities (Modified Brief Pain Inventory) | In past 24 hours, pain interfered with ability to function or perform activity (0-10 numeric scale, 0=no interference) | 1 to 5 days post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-operative pain, hernia surgery, opioid