Bupivacaine Effectiveness and Safety in SABER® Trial

Phase 3

Completed

Conditions: Postoperative Pain
Abdominal Surgery

Interventions: Drug: SABER-Bupivacaine
Drug: SABER-Placebo
Drug: Bupivacaine HCl

Registration Number: NCT01052012

Lead Sponsor: Durect

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 (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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 331

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of systemic steroids, anticonvulsants, antiepileptics, antidepressants, or monoamine oxidase inhibitors, who cannot be withdrawn from these medications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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active: SABER-Bupivacaine	SABER-Bupivacaine	SABER-Bupivacaine
Placebo: SABER-Placebo	SABER-Placebo	SABER-Placebo
Comparator: Bupivacaine HCl	Bupivacaine HCl	Bupivacaine HCl

Primary Outcome Measures

Name	Time	Method
Mean Pain Intensity on Movement	0 to 72 hours post-dose	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.
Supplemental Opioid Use	0-72 hours post dose	Total morphine-equivalent dose during 0-72 hours post dose. Median values were presented because data was not normally distributed.

Secondary Outcome Measures

Name	Time	Method
Total Morphine-equivalent Dose	0-48 hours post dose	Total morphine-equivalent dose during 0-48 hours post dose.
Proportion (Percent) of Patients Who Have Evidence of a Wound Infection	0 to 14 days post-dose (Visits 3 and 4)	From Surgical Wound Healing and Local Tissue Condition Evaluation
Time-to-first Use of Opioid Rescue Medication	0 to 14 days post-dose (Time from extubation until first opioid use)
Pain Intensity at Rest AUC During 0-72 Hours Post Dose	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.
Mean Pain Intensity on Movement	0 to 48 hours post-dose	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.
Number (Incidence) of Participants With Opioid-related Side Effects	0 to 30 days post-dose	AEs include: nausea, vomiting, constipation, dizziness, somnolence, urinary retention, respiratory depression
Mean Pain Intensity at Rest AUC During 0-48 Hours Post Dose	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.