Hernia, Postoperative Pain, Surgery
Conditions
Keywords
Post-operative pain, hernia 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. 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.
Interventions
Injectable Extended Release Solution; 2.5 mL SABER-Bupivacaine/Once
DRUGSABER-Placebo
Injectable Solution; 2.5 or 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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity on Movement | 1 to 72 hours post-dose | 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. |
| Proportion (Percent) of Patients Using Supplemental Opioids | 0 to 14 days post-dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity | 1 to 48 hours post-dose | 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. |
| Treatment Satisfaction | 1 to 5 days post-dose | 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). |
| Supplemental Opioid Use | 0 to 14 days post-dose | — |
| Mean Function Activities (Modified Brief Pain Inventory) | 1 to 5 days post-dose | In past 24 hours, pain interfered with ability to function or perform activity (0-10 numeric scale, 0=no interference) |
Countries
Australia, New Zealand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: SABER-Bupivacaine 2.5 mL SABER-Bupivacaine/Once
SABER-Bupivacaine: Injectable Extended Release Solution; 2.5 mL SABER-Bupivacaine(330 mg)/Once | 44 |
| Group 2: SABER-Bupivacaine 5.0 mL SABER-Bupivacaine/Once
SABER-Bupivacaine: Injectable Extended Release Solution; 5.0 mL SABER-Bupivacaine(660 mg)/Once | 47 |
| Group 3: SABER-Placebo 2.5 mL or 5.0 mL SABER-Placebo/Once
SABER-Placebo: Injectable Solution; 2.5 or 5.0 mL SABER-Placebo/Once | 32 |
| Total | 123 |
Baseline characteristics
| Characteristic | Group 1: SABER-Bupivacaine | Group 2: SABER-Bupivacaine | Group 3: SABER-Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 45.9 years STANDARD_DEVIATION 11.82 | 48.6 years STANDARD_DEVIATION 13.04 | 50.3 years STANDARD_DEVIATION 9.26 | 48.11 years STANDARD_DEVIATION 11.76 |
| BMI | 26.5 kg/m^2 STANDARD_DEVIATION 3.74 | 26.3 kg/m^2 STANDARD_DEVIATION 2.92 | 26.9 kg/m^2 STANDARD_DEVIATION 3.68 | 26.55 kg/m^2 STANDARD_DEVIATION 3.41 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 42 Participants | 45 Participants | 32 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 47 | 0 / 32 |
| other Total, other adverse events | 44 / 44 | 44 / 47 | 31 / 32 |
| serious Total, serious adverse events | 3 / 44 | 2 / 47 | 1 / 32 |
Outcome results
Primary
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.
Time frame: 1 to 72 hours post-dose
Population: ITT population (patients with data available)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SABER-Bupivacaine | Pain Intensity on Movement | 3.4 score on a scale | Standard Error 0.26 |
| Group 2: SABER-Bupivacaine | Pain Intensity on Movement | 2.7 score on a scale | Standard Error 0.25 |
| Group 3: SABER-Placebo | Pain Intensity on Movement | 3.9 score on a scale | Standard Error 0.29 |
Comparison: Pain Intensity on Movement AUCs1-72 hours Including Pain Assessed Upon Taking Opioid Rescue - ITTp-value: 0.003195% CI: [-1.84, -0.44]ANOVA
Primary
Proportion (Percent) of Patients Using Supplemental Opioids
Time frame: 0 to 14 days post-dose
Population: ITT population (patients with data available)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: SABER-Bupivacaine | Proportion (Percent) of Patients Using Supplemental Opioids | 31 Participants |
| Group 2: SABER-Bupivacaine | Proportion (Percent) of Patients Using Supplemental Opioids | 25 Participants |
| Group 3: SABER-Placebo | Proportion (Percent) of Patients Using Supplemental Opioids | 23 Participants |
Comparison: Proportion of Patients Not Taking Any Supplemental Opioid Analgesic Medicationp-value: 0.0909Cochran-Mantel-Haenszel
Secondary
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)
Time frame: 1 to 5 days post-dose
Population: ITT population (patients with data available)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 1) | 1.1 score on a scale | Standard Deviation 2.08 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 2) | 3.0 score on a scale | Standard Deviation 2.37 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 3) | 2.5 score on a scale | Standard Deviation 2.09 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 4) | 1.7 score on a scale | Standard Deviation 1.88 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 5) | 1.7 score on a scale | Standard Deviation 1.83 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 1) | 3.5 score on a scale | Standard Deviation 2.76 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 2) | 2.8 score on a scale | Standard Deviation 2.25 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 3) | 2.5 score on a scale | Standard Deviation 2.02 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 4) | 2.0 score on a scale | Standard Deviation 1.9 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 5) | 1.8 score on a scale | Standard Deviation 1.89 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 1) | 3.2 score on a scale | Standard Deviation 2.56 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 2) | 1.0 score on a scale | Standard Deviation 1.56 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 3) | 0.7 score on a scale | Standard Deviation 1.22 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 4) | 0.7 score on a scale | Standard Deviation 1.33 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 5) | 0.5 score on a scale | Standard Deviation 1.17 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 1) | 2.7 score on a scale | Standard Deviation 2.37 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 2) | 2.0 score on a scale | Standard Deviation 2.25 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 3) | 1.5 score on a scale | Standard Deviation 1.61 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 4) | 1.4 score on a scale | Standard Deviation 2.03 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 5) | 1.1 score on a scale | Standard Deviation 1.52 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 1) | 2.6 score on a scale | Standard Deviation 2.49 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 2) | 2.0 score on a scale | Standard Deviation 2.26 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 3) | 1.4 score on a scale | Standard Deviation 1.67 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 4) | 1.2 score on a scale | Standard Deviation 1.71 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 5) | 1.1 score on a scale | Standard Deviation 1.5 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 1) | 1.2 score on a scale | Standard Deviation 1.89 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 2) | 0.9 score on a scale | Standard Deviation 1.61 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 3) | 0.5 score on a scale | Standard Deviation 1.06 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 4) | 0.4 score on a scale | Standard Deviation 1.11 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 5) | 0.3 score on a scale | Standard Deviation 0.98 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 1) | 1.5 score on a scale | Standard Deviation 2.51 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 2) | 1.2 score on a scale | Standard Deviation 2.06 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 3) | 1.4 score on a scale | Standard Deviation 2.39 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 4) | 1.1 score on a scale | Standard Deviation 1.93 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 5) | 0.8 score on a scale | Standard Deviation 1.86 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 1) | 4.4 score on a scale | Standard Deviation 3.41 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 2) | 4.4 score on a scale | Standard Deviation 3.1 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 3) | 3.9 score on a scale | Standard Deviation 3.08 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 4) | 3.2 score on a scale | Standard Deviation 2.76 |
| Group 1: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 5) | 3.0 score on a scale | Standard Deviation 2.77 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 4) | 0.4 score on a scale | Standard Deviation 0.73 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 2) | 0.8 score on a scale | Standard Deviation 1.43 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 5) | 0.4 score on a scale | Standard Deviation 0.74 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 1) | 2.0 score on a scale | Standard Deviation 2.31 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 3) | 2.9 score on a scale | Standard Deviation 2.28 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 2) | 1.3 score on a scale | Standard Deviation 1.61 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 3) | 0.5 score on a scale | Standard Deviation 1.06 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 3) | 0.9 score on a scale | Standard Deviation 1.14 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 4) | 0.6 score on a scale | Standard Deviation 1.14 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 5) | 0.5 score on a scale | Standard Deviation 0.74 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 4) | 0.5 score on a scale | Standard Deviation 0.9 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 1) | 2.2 score on a scale | Standard Deviation 2.58 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 2) | 1.4 score on a scale | Standard Deviation 1.79 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 5) | 2.2 score on a scale | Standard Deviation 1.97 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 3) | 0.7 score on a scale | Standard Deviation 1.01 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 5) | 0.4 score on a scale | Standard Deviation 0.86 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 4) | 0.5 score on a scale | Standard Deviation 0.9 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 5) | 0.7 score on a scale | Standard Deviation 0.92 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 4) | 2.3 score on a scale | Standard Deviation 2.02 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 1) | 0.4 score on a scale | Standard Deviation 0.94 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 1) | 3.8 score on a scale | Standard Deviation 3.1 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 2) | 0.3 score on a scale | Standard Deviation 0.72 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 1) | 2.7 score on a scale | Standard Deviation 2.63 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 2) | 2.4 score on a scale | Standard Deviation 1.88 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 3) | 0.2 score on a scale | Standard Deviation 0.55 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 3) | 1.5 score on a scale | Standard Deviation 1.71 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 4) | 1.1 score on a scale | Standard Deviation 1.27 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 5) | 1.1 score on a scale | Standard Deviation 1.33 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 4) | 0.2 score on a scale | Standard Deviation 0.46 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 1) | 2.7 score on a scale | Standard Deviation 2.74 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 2) | 2.3 score on a scale | Standard Deviation 2.09 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 2) | 3.4 score on a scale | Standard Deviation 2.61 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 3) | 1.4 score on a scale | Standard Deviation 1.62 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 5) | 0.1 score on a scale | Standard Deviation 0.36 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 4) | 1.0 score on a scale | Standard Deviation 1.29 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 5) | 1.3 score on a scale | Standard Deviation 1.47 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 1) | 0.7 score on a scale | Standard Deviation 1.32 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 1) | 0.7 score on a scale | Standard Deviation 1.27 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 2) | 1.0 score on a scale | Standard Deviation 1.62 |
| Group 2: SABER-Bupivacaine | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 3) | 0.4 score on a scale | Standard Deviation 0.84 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 2) | 0.5 score on a scale | Standard Deviation 1.04 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 4) | 0.5 score on a scale | Standard Deviation 1.21 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 1) | 1.4 score on a scale | Standard Deviation 1.59 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 1) | 4.6 score on a scale | Standard Deviation 3.49 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 5) | 0.3 score on a scale | Standard Deviation 0.61 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 2) | 1.1 score on a scale | Standard Deviation 1.82 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 1) | 5.7 score on a scale | Standard Deviation 3.06 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 1) | 2.6 score on a scale | Standard Deviation 2.09 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 3) | 1.5 score on a scale | Standard Deviation 1.77 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 2) | 3.0 score on a scale | Standard Deviation 2.5 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 2) | 1.8 score on a scale | Standard Deviation 1.92 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 5) | 3.1 score on a scale | Standard Deviation 2.71 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 3) | 0.6 score on a scale | Standard Deviation 0.63 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 3) | 1.2 score on a scale | Standard Deviation 1.31 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 3) | 0.7 score on a scale | Standard Deviation 1.28 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 3) | 2.1 score on a scale | Standard Deviation 2.01 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 4) | 1.3 score on a scale | Standard Deviation 2.21 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 3) | 4.5 score on a scale | Standard Deviation 3.12 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 3) | 0.4 score on a scale | Standard Deviation 1.19 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Fall Asleep (Day 5) | 0.8 score on a scale | Standard Deviation 1.45 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 4) | 1.7 score on a scale | Standard Deviation 2.45 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 4) | 1.9 score on a scale | Standard Deviation 2.12 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 1) | 2.1 score on a scale | Standard Deviation 2.28 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 4) | 0.7 score on a scale | Standard Deviation 1.56 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 4) | 3.5 score on a scale | Standard Deviation 2.97 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 2) | 1.8 score on a scale | Standard Deviation 2.01 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 5) | 0.3 score on a scale | Standard Deviation 0.86 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | get out of bed (Day 5) | 1.4 score on a scale | Standard Deviation 1.6 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 3) | 1.2 score on a scale | Standard Deviation 1.5 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Interact With Visitors (Day 2) | 1.1 score on a scale | Standard Deviation 1.31 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 5) | 1.3 score on a scale | Standard Deviation 1.46 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 4) | 1.3 score on a scale | Standard Deviation 2.33 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 5) | 0.4 score on a scale | Standard Deviation 0.69 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 1) | 3.9 score on a scale | Standard Deviation 3.14 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Stay Asleep (Day 5) | 0.7 score on a scale | Standard Deviation 1.43 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 4) | 0.3 score on a scale | Standard Deviation 0.86 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Cough (Day 2) | 5.0 score on a scale | Standard Deviation 2.99 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Eat (Day 1) | 0.9 score on a scale | Standard Deviation 1.58 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability to walk (Day 2) | 2.3 score on a scale | Standard Deviation 2.35 |
| Group 3: SABER-Placebo | Mean Function Activities (Modified Brief Pain Inventory) | Ability To Deep Breath (Day 1) | 1.5 score on a scale | Standard Deviation 2.32 |
Secondary
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.
Time frame: 1 to 48 hours post-dose
Population: ITT population (patients with data available)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SABER-Bupivacaine | Pain Intensity | 3.4 score on a scale | Standard Error 0.26 |
| Group 2: SABER-Bupivacaine | Pain Intensity | 2.8 score on a scale | Standard Error 0.26 |
| Group 3: SABER-Placebo | Pain Intensity | 4.1 score on a scale | Standard Error 0.3 |
Secondary
Supplemental Opioid Use
Time frame: 0 to 14 days post-dose
Population: ITT population (patients with data available)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: SABER-Bupivacaine | Supplemental Opioid Use | 17.7 Total morphine equivalent dose (mg) | Standard Deviation 25.36 |
| Group 2: SABER-Bupivacaine | Supplemental Opioid Use | 12.5 Total morphine equivalent dose (mg) | Standard Deviation 17.63 |
| Group 3: SABER-Placebo | Supplemental Opioid Use | 38.4 Total morphine equivalent dose (mg) | Standard Deviation 60.24 |
Secondary
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).
Time frame: 1 to 5 days post-dose
Population: ITT population (patients with data available)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 3 | Very Satisfied | 26 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 1 | Slightly Dissatisfied | 1 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 1 | Very Satisfied | 21 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 3 | Satisfied | 13 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 2 | Slightly Dissatisfied | 1 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 5 | Slightly Dissatisfied | 1 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 3 | Slightly Satisfied | 3 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 2 | Slightly Satisfied | 4 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 4 | Satisfied | 18 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 3 | Slightly Dissatisfied | 0 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 2 | Satisfied | 15 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 4 | Very Satisfied | 18 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 3 | Dissatisfied | 0 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 2 | Very Satisfied | 21 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 1 | Satisfied | 15 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 3 | Very Dissatisfied | 0 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 4 | Slightly Satisfied | 2 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 5 | Very Dissatisfied | 0 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 5 | Satisfied | 16 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 4 | Slightly Dissatisfied | 0 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 5 | Dissatisfied | 0 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 2 | Very Dissatisfied | 0 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 4 | Dissatisfied | 0 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 1 | Slightly Satisfied | 2 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 5 | Very Satisfied | 21 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 1 | Very Dissatisfied | 2 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 5 | Slightly Satisfied | 1 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 4 | Very Dissatisfied | 0 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 1 | Dissatisfied | 1 Participants |
| Group 1: SABER-Bupivacaine | Treatment Satisfaction | Day 2 | Dissatisfied | 1 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 3 | Slightly Satisfied | 2 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 1 | Satisfied | 16 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 1 | Very Satisfied | 21 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 2 | Very Dissatisfied | 0 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 2 | Dissatisfied | 0 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 4 | Very Satisfied | 22 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 5 | Very Dissatisfied | 0 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 5 | Dissatisfied | 0 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 1 | Slightly Satisfied | 4 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 1 | Very Dissatisfied | 2 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 1 | Dissatisfied | 0 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 1 | Slightly Dissatisfied | 2 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 2 | Slightly Dissatisfied | 2 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 2 | Slightly Satisfied | 3 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 2 | Satisfied | 19 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 2 | Very Satisfied | 19 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 3 | Very Dissatisfied | 0 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 3 | Dissatisfied | 0 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 3 | Slightly Dissatisfied | 0 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 3 | Satisfied | 23 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 3 | Very Satisfied | 20 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 4 | Very Dissatisfied | 0 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 4 | Dissatisfied | 0 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 4 | Slightly Dissatisfied | 0 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 4 | Slightly Satisfied | 1 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 4 | Satisfied | 21 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 5 | Slightly Dissatisfied | 0 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 5 | Slightly Satisfied | 1 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 5 | Satisfied | 17 Participants |
| Group 2: SABER-Bupivacaine | Treatment Satisfaction | Day 5 | Very Satisfied | 24 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 3 | Satisfied | 14 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 1 | Dissatisfied | 2 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 5 | Slightly Dissatisfied | 1 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 3 | Very Satisfied | 11 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 1 | Very Dissatisfied | 0 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 2 | Very Dissatisfied | 1 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 4 | Very Dissatisfied | 0 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 5 | Dissatisfied | 0 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 1 | Satisfied | 12 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 4 | Dissatisfied | 1 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 5 | Very Dissatisfied | 0 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 5 | Slightly Satisfied | 1 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 4 | Slightly Dissatisfied | 0 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 4 | Very Satisfied | 13 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 1 | Very Satisfied | 11 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 4 | Slightly Satisfied | 3 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 2 | Very Satisfied | 11 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 4 | Satisfied | 12 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 3 | Very Dissatisfied | 0 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 2 | Satisfied | 12 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 5 | Very Satisfied | 14 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 3 | Dissatisfied | 0 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 2 | Slightly Satisfied | 4 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 2 | Dissatisfied | 0 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 3 | Slightly Dissatisfied | 1 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 2 | Slightly Dissatisfied | 2 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 1 | Slightly Satisfied | 4 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 3 | Slightly Satisfied | 2 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 1 | Slightly Dissatisfied | 0 Participants |
| Group 3: SABER-Placebo | Treatment Satisfaction | Day 5 | Satisfied | 11 Participants |