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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
  • Queensland
    • Kippa Ring, Queensland, Australia, 4021
  • South Australia
    • Adelaide, South Australia, Australia, 5000
    • Toorak Gardens, South Australia, Australia, 5065
  • Victoria
    • Geelong, Victoria, Australia, 3220
    • Hampton, Victoria, Australia, 3188
    • Ringwood East, Victoria, Australia, 3135
• New Zealand
  • Christchurch, New Zealand
  • Hamilton, New Zealand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (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 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Durect
• Collaborators: Nycomed
• Investigators: Study Director: Dmitri Lissin, MD, Durect

Publications and helpful links

General Publications

• Hadj A, Hadj A, Hadj A, Rosenfeldt F, Nicholson D, Moodie J, Turner R, Watts R, Fletcher I, Abrouk N, Lissin D. Safety and efficacy of extended-release bupivacaine local anaesthetic in open hernia repair: a randomized controlled trial. ANZ J Surg. 2012 Apr;82(4):251-7. doi: 10.1111/j.1445-2197.2011.05754.x. Epub 2011 Jun 24.

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: January 5, 2009
• First Submitted That Met QC Criteria: January 6, 2009
• First Posted (Estimate): January 7, 2009

Study Record Updates

• Last Update Posted (Actual): June 1, 2021
• Last Update Submitted That Met QC Criteria: May 7, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: opioid; Postoperative pain; shoulder surgery
• 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: C803-017