Postoperative Pain
Conditions
Keywords
Postoperative pain, shoulder surgery, opioid
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 (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.
Interventions
Injectable Extended Release Solution; 5.0 mL SABER-Bupivacaine/Once
DRUGSABER-Placebo
Injectable Solution; 5.0 mL SABER-Placebo/Once
Sponsors
Nycomed
Durect
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Pain Intensity on Movement AUC (Time Normalized Area Under the Curve) During the Period 0 to 72 Hours Post-dose. | 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. |
| Supplemental Opioid Use | 0 to 72 hours post-dose | Mean total morphine-equivalent dose during the period 0 to 72 hours post-dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Supplemental Opioid Use | 0 to 48 hours post-dose | Mean total morphine-equivalent dose during the period 0 to 48 hours post-dose (0 to 2 days post-dose) |
| Number (Frequency) of Participants Reporting Opioid-related Adverse Events | 0 to 72 hours post-dose | 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. |
| Severity of Opioid-related Side Effects | 0 to 14 days post-dose | — |
| Time-to-first Use of Opioid Supplemental Pain Medication | 0 to 14 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). | 0 to 48 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). 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. |
Countries
Australia, New Zealand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: SABER-Bupivacaine 5.0 mL SABER-Bupivacaine/Once
SABER-Bupivacaine: Injectable Extended Release Solution; 5.0 mL SABER-Bupivacaine/Once | 40 |
| Group 2: SABER-Placebo 5.0 mL SABER-Placebo/Once
SABER-Placebo: Injectable Solution; 5.0 mL SABER-Placebo/Once | 20 |
| Total | 60 |
Baseline characteristics
| Characteristic | Group 1: SABER-Bupivacaine | Group 2: SABER-Placebo | Total |
|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 8.8 | 47.6 years STANDARD_DEVIATION 9.9 | 47.5 years STANDARD_DEVIATION 9.1 |
| BMI | 26.57 kg/m^2 STANDARD_DEVIATION 4.17 | 29.33 kg/m^2 STANDARD_DEVIATION 5.08 | 27.49 kg/m^2 STANDARD_DEVIATION 4.64 |
| Sex: Female, Male Female | 23 Participants | 10 Participants | 33 Participants |
| Sex: Female, Male Male | 17 Participants | 10 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 20 |
| other Total, other adverse events | 38 / 40 | 19 / 20 |
| serious Total, serious adverse events | 1 / 40 | 0 / 20 |
Outcome results
Primary
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.
Time frame: 0 to 72 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SABER-Bupivacaine | Mean Pain Intensity on Movement AUC (Time Normalized Area Under the Curve) During the Period 0 to 72 Hours Post-dose. | 5.35 score on a scale | Standard Deviation 1.91 |
| Group 2: SABER-Placebo | Mean Pain Intensity on Movement AUC (Time Normalized Area Under the Curve) During the Period 0 to 72 Hours Post-dose. | 5.81 score on a scale | Standard Deviation 2.25 |
p-value: 0.30395% CI: [-1.74, 0.47]ANCOVA
Primary
Supplemental Opioid Use
Mean total morphine-equivalent dose during the period 0 to 72 hours post-dose
Time frame: 0 to 72 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SABER-Bupivacaine | Supplemental Opioid Use | 44.54 mg | Standard Deviation 29.62 |
| Group 2: SABER-Placebo | Supplemental Opioid Use | 49.94 mg | Standard Deviation 45.69 |
p-value: 0.30395% CI: [-30.04, 9.55]ANCOVA
Secondary
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.
Time frame: 0 to 48 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SABER-Bupivacaine | Mean Pain Intensity on Movement AUC (Time-normalized AUC) During the Period 0 to 48 Hours Post-dose (0 to 2 Days Post-dose). | 5.65 score on a scale | Standard Deviation 2.07 |
| Group 2: SABER-Placebo | Mean Pain Intensity on Movement AUC (Time-normalized AUC) During the Period 0 to 48 Hours Post-dose (0 to 2 Days Post-dose). | 6.14 score on a scale | Standard Deviation 2.23 |
Secondary
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.
Time frame: 0 to 72 hours post-dose
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Constipation | 10 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Respiratory Depression | 3 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Dizziness | 4 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Dizziness | 7 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Drowsiness | 13 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Dizziness | 14 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Nausea | 8 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Drowsiness | 18 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Respiratory Depression | 0 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Urinary Retention | 6 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Urinary Retention | 1 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Nausea | 10 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Vomiting | 1 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Nausea | 17 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Constipation | 9 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Respiratory Depression | 0 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Dizziness | 1 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Vomiting | 12 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Drowsiness | 10 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Urinary Retention | 3 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Nausea | 4 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Drowsiness | 20 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Respiratory Depression | 0 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Vomiting | 3 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Urinary Retention | 1 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Constipation | 5 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Vomiting | 0 Participants |
| Group 1: SABER-Bupivacaine | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Constipation | 0 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Vomiting | 0 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Constipation | 0 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Dizziness | 6 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Drowsiness | 12 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Nausea | 11 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Respiratory Depression | 0 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Urinary Retention | 1 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 0 : Vomiting | 4 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Constipation | 1 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Dizziness | 4 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Drowsiness | 7 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Nausea | 5 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Respiratory Depression | 0 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Urinary Retention | 2 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 1 : Vomiting | 2 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Constipation | 5 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Dizziness | 3 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Drowsiness | 8 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Nausea | 2 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Respiratory Depression | 0 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Urinary Retention | 1 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 2 : Vomiting | 0 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Constipation | 4 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Dizziness | 0 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Drowsiness | 2 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Nausea | 1 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Respiratory Depression | 0 Participants |
| Group 2: SABER-Placebo | Number (Frequency) of Participants Reporting Opioid-related Adverse Events | Day 3 : Urinary Retention | 0 Participants |
Secondary
Severity of Opioid-related Side Effects
Time frame: 0 to 14 days post-dose
Population: Severity of opioid related side effects were not collected in the opioid related side effects diary.
Secondary
Supplemental Opioid Use
Mean total morphine-equivalent dose during the period 0 to 48 hours post-dose (0 to 2 days post-dose)
Time frame: 0 to 48 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SABER-Bupivacaine | Supplemental Opioid Use | 37.13 mg | Standard Deviation 23.4 |
| Group 2: SABER-Placebo | Supplemental Opioid Use | 43.70 mg | Standard Deviation 37.44 |
Secondary
Time-to-first Use of Opioid Supplemental Pain Medication
Time frame: 0 to 14 days post-dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: SABER-Bupivacaine | Time-to-first Use of Opioid Supplemental Pain Medication | 0.43 hours |
| Group 2: SABER-Placebo | Time-to-first Use of Opioid Supplemental Pain Medication | 0.48 hours |