Bupivacaine Effectiveness and Safety in SABER® Trial (BESST)

Bupivacaine Effectiveness and Safety in SABER Trial (BESST)

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain; Abdominal Surgery
• Intervention / Treatment: Drug: SABER-Bupivacaine; Drug: Bupivacaine HCl; Drug: SABER-Placebo

• Study Type: Interventional
• Enrollment (Actual): 331
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • DURECT Study Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • DURECT Study Site
    • Ringwood East, Victoria, Australia, 3135
      • DURECT Study Site
• New Zealand
  • Christchurch, New Zealand, 8022
    • DURECT Study Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • DURECT Study Site
    • Florence, Alabama, United States, 35630
      • DURECT Study Site
    • Mobile, Alabama, United States, 36608
      • DURECT Study Site
    • Mobile, Alabama, United States, 36617
      • DURECT Study Site
    • Montgomery, Alabama, United States, 36106
      • DURECT Study Site
    • Sheffield, Alabama, United States, 35660
      • DURECT Study Site
  • California
    • Arcadia, California, United States, 91007
      • DURECT Study Site
    • Fontana, California, United States, 92335
      • DURECT Study Site
    • Laguna Hills, California, United States, 92653
      • DURECT Study Site
    • Pasadena, California, United States, 91105
      • DURECT Study Site
  • Florida
    • Tampa, Florida, United States, 33606
      • DURECT Study Site
  • Georgia
    • Powder Springs, Georgia, United States, 30127
      • DURECT Study Site
  • Indiana
    • Indianapolis, Indiana, United States, 46206
      • DURECT Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • DURECT Study Site
  • Michigan
    • Troy, Michigan, United States, 48085
      • DURECT Study Site
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • DURECT Study Site
  • New York
    • New York, New York, United States, 10016
      • DURECT Study Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • DURECT Study Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • DURECT Study Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • DURECT Study Site
  • Texas
    • Houston, Texas, United States, 77024
      • DURECT Study Site
    • Temple, Texas, United States, 77375
      • DURECT Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active: SABER-Bupivacaine; SABER-Bupivacaine	Drug: SABER-Bupivacaine; Injectable Extended Release Solution; SABER-Bupivacaine /Once; Other Names: POSIMIR® bupivacaine solution
Active Comparator: Comparator: Bupivacaine HCl; Bupivacaine HCl	Drug: Bupivacaine HCl; Injectable Solution; Bupivacaine HCl /Once
Placebo Comparator: Placebo: SABER-Placebo; SABER-Placebo	Drug: SABER-Placebo; Injectable Solution; SABER-Placebo/Once

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Durect
• Collaborators: Hospira, now a wholly owned subsidiary of Pfizer; Nycomed
• Investigators: Study Director: Dmitri Lissin, MD, Durect

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: January 18, 2010
• First Submitted That Met QC Criteria: January 18, 2010
• First Posted (Estimate): January 20, 2010

Study Record Updates

• Last Update Posted (Actual): June 1, 2021
• Last Update Submitted That Met QC Criteria: May 6, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Laparoscopic surgery; Opioid; Local anesthetic; Post-operative pain; Bupivacaine; Postoperative pain
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: C803-025