Bunionectomy, Hallux Valgus
Conditions
Keywords
EXPAREL, Bupivacaine, Analgesia
Brief summary
The study is conducted sequentially in two parts. Part A: The purpose is to obtain information on pharmacokinetic (PK) profile, pharmacodynamics (PD), efficacy, safety, and to assess the performance of 266 mg EXPAREL vs 133 mg EXPAREL. Part B: The purpose is to evaluate the efficacy and safety of the preferred dosage of EXPAREL from Part A compared with bupivacaine HCl.
Detailed description
This is a Phase 3, multicenter, randomized, double-blind, active controlled study in approximately 180 subjects undergoing bunionectomy. The study will be conducted in two parts (Part A and Part B). Part A will be completed and analyzed before enrollment in Part B is initiated. Subjects may be screened up to 45 days prior to the day of surgery but eligibility must be re-confirmed on the day of surgery prior to randomization. The following screening procedures will be performed after the informed consent form (ICF) is signed (if not standard of care): assess eligibility, record medical/surgical history, record prior and concomitant medications, record demographics and baseline characteristics, record subject height and weight for body mass index (BMI) calculation, assess chronic opioid use in the past 30 days, conduct urine pregnancy test for women of childbearing potential, perform 12-lead EKG, record serious adverse events (SAEs) starting when the ICF is signed, and record medications for treatment of SAEs. On Day 1, prior to sciatic nerve block, study staff will review Pain Rating Guide with the subject and record their responses to: * Numeric rating scale (NRS) score on the worst pain of their operative foot in the last 30 days. * NRS score on the average pain of their operative foot in the last 30 days. Part A will enroll approximately 60 subjects undergoing bunionectomy into 1 of 3 arms. They will be randomized 1:1:1 to either EXPAREL 266 mg, EXPAREL 133 mg, or 0.25% bupivacaine HCl (50mg). Part A subjects will be asked to perform sensory function assessments, perform motor function assessments and obtain PK samples. Based on the findings of the interim analysis after completion of Part A, the study may stop for futility or proceed to Part B. Part B is a 2-arm study with 120 subjects being randomized 1:1 to either the better performing dosage of EXPAREL from Part A (266mg or 133mg) or 0.25% bupivacaine HCl (50mg). All eligible subjects will receive Celecoxib 200 mg, orally (PO) pre-operatively within four hours prior to surgery. Part A: On Day 1, Subjects will be randomized (1:1:1) to receive a sciatic (in the popliteal fossa) nerve block with a single dose of either: EXPAREL 266 mg, EXPAREL 133 mg, or 0.25% bupivacaine HCl (50 mg). Part B: will continue enrolling with one of the EXPAREL arms (EXPAREL 266 mg arm or EXPAREL 133 mg arm) and the bupivacaine HCl arm. Therefore, the EXPAREL study arm that fails to show efficacy (conditional power less than 30% in the Part A analysis) will be dropped and the study will continue with two study arms. The final analysis will include subjects from both Part A and Part B. 1. If the conditional power of one EXPAREL arm is less than 30% and the other EXPAREL arm is greater than or equal to 30%: * The EXPAREL arm with conditional power less than 30% will be dropped in Part B. 2. If both EXPAREL arms have a conditional power greater than or equal to 30%: * If the conditional power of the 266 mg EXPAREL arm is more than 10% greater than the conditional power of the 133 mg EXPAREL arm, then the 266 mg EXPAREL arm will be kept and the 133 mg EXPAREL arm will be dropped. Otherwise, the 133 mg EXPAREL arm will be kept and the 266 mg EXPAREL arm will be dropped in Part B. 3. If the conditional power of both treatment arms is less than 30%: * The study will stop for futility All subjects will receive a dose of 1000 mg of intravenous (IV) acetaminophen at the time of surgical incision. All subjects will receive one post-operative dose of 1000 mg IV acetaminophen, administered approximately 8 hours after the first dose (approximately 8 hours after incision). The maximum total dose will not exceed 2000 mg. No additional acetaminophen is permitted after the second IV acetaminophen dose. Medications will be administered on an as needed (PRN) basis; opioids should not be given on a predetermined schedule. After 96 hours, the analgesic regimen may be adjusted for each subject individually as deemed appropriate by the physician responsible for postsurgical care. NRS Pain intensity scores (for pain experiencing in operative foot right now, for the worst pain experienced in the operative foot in the last 24 hours, and for the average pain in the operative foot in the last 24 hours) will be asked from the end of surgery to 96 hours post-surgery at designated timepoints. Subjects in Part A and Part B will be discharged after the completion of the 168h and 96h assessments, respectively. For the assessment of adverse events (AEs), SAEs, and concomitant medication use, a follow-up phone call will be made on Post Surgery Day (POD) 14 (±3 days).
Interventions
DRUGBupivacaine liposome injectable suspension 266 mg
Sciatic nerve block in the popliteal fossa with EXPAREL 266 mg
DRUGBupivacaine HCl
Sciatic nerve block in the popliteal fossa with Bupivacaine HCl
DRUGBupivacaine liposome injectable suspension 133 mg
Sciatic nerve block in the popliteal fossa with EXPAREL 133 mg
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Individuals preparing and administering study drug, or transporting unblinded drug will not be allowed to perform any of the study assessments after randomization (with the possible logistical exception of drawing blood in the operating room (OR) to be processed by blinded staff for the PK assessments) or reveal the assigned study treatment to any other members of the study team at any time. Additionally, efforts will be made to prevent the subject from observing the study drug syringe. Staff members conducting study-specific, postsurgical assessments and the subjects will remain blinded to the assigned treatment throughout the study in part by not being present during the administration of the nerve block. The site PI must be blinded to the study drug and will not be involved in and/or present during study drug administration. No crossover will be permitted between the blinded and unblinded study personnel throughout the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, ages 18 or older at screening 2. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3 3. Able to provide informed consent, adhere to the study schedule, and complete all study assessments 4. Primary surgical indication is related to a bunion deformity (i.e., hallux valgus) and subject is scheduled to undergo a distal metaphyseal osteotomy procedure (e.g., Austin procedure as opposed to Lapiplasty, Lapidus bunionectomies or base wedge bunionectomies) 5. Indicated to undergo elective (i.e., not emergency) bunionectomy 6. Body Mass Index (BMI) ≥18 and \<40 kg/m2
Exclusion criteria
1. Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (e.g., amide-type local anesthetics, opioids, bupivacaine HCl, NSAIDs) 2. Concurrent painful physical condition (e.g. arthritis, fibromyalgia, cancer) that may require analgesic treatment with NSAIDs or opioids in the post dosing period for pain that is not strictly related to the foot surgery and which, in the Investigator's opinion, may confound the post dosing assessments 3. Inadequate sensory function of the foot/ankle as assessed by the Investigator 4. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years 5. Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study 6. Previous participation in an EXPAREL study 7. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, could interfere with study assessments or compliance 8. Currently pregnant, nursing, or planning to become pregnant during the study 9. Clinically significant medical disease that, in the opinion of the Investigator, would make participation in a clinical study inappropriate. This includes diabetic neuropathy, coagulation or bleeding disorders, severe peripheral vascular disease, renal insufficiency, hepatic dysfunction or other conditions that would constitute a contraindication to participation in the study 10. Currently on a neuromodulating agent (e.g., gabapentin, pregabalin \[Lyrica\], duloxetine \[Cymbalta\], etc.) 11. Current use of systemic glucocorticoids within 30 days of randomization in this study 12. Use of dexmedetomidine HCl (Precedex®) or clonidine within 3 days of study drug administration 13. Any use of marijuana (including tetrahydrocannabinol (THC) and cannabidiol (CBD)) within 30 days prior to randomization, or planned use during the course of the study 14. Chronic opioid use within 30 days prior to randomization (average ≥30 oral morphine equivalents/day)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NRS Pain Scores Through 96 Hours Post-surgery | 0- 96 hours post-surgery | The numeric rating scale pain intensity scores ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 96 hours post-surgery. For each subject, the area under the curve was derived using the trapezoidal rule on the pain scores adjusted for opioid pain medication using the observed and imputed values. Area under the curve started with the first pain assessment obtained after surgery and use all subsequent pain assessments up to 96 hours post-surgery. Pain scores were taken at 5 interval point 0 hours, 24 hours, 48 hours, 72 hours, and 96 hours. There were also unscheduled pain scores measured before opioid consumption also included in the area under the curve calculation. The area under the curve ranged from 0 to 960. Higher scores represent a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postsurgical Opioid Consumption Through 96 Hours Post-surgery | 0 to 96 hours post-surgery | Total postsurgical opioid consumption in oral morphine equivalents (OMED) from 0 to 96 hours post-surgery |
| Opioid-free Subjects Through 96 Hours Post-surgery | 0 to 96 hours post-surgery | Percentage of opioid-free subjects through 96 hours |
| First Opioid Consumption Post-surgery | 0 to 96 hours post-surgery | Time to first opioid consumption post-surgery |
| NRS Pain Scores Post-surgery | 0-24 hours, 24-48 hours, 48-72 hours, and 72-96 hours post-surgery | Worst and average NRS pain intensity scores at 24h, 48h, 72h, and 96h from the end of surgery Worst and average pain intensity scores on a numeric rating scale ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours. Mean scores at each timepoint are provided. The total range is 0 (no pain) to 10 (worst possible pain). Higher values on the scale represent worse outcome. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited based on physician referral at 6 sites between February 2022 and April 2022 for Part A and between April 2022 and July 2022 for Part B. The first participant was enrolled on February 15, 2022 and the last participant was enrolled on July 18, 2022.
Pre-assignment details
Of 452 screened participants, 185 met inclusion criteria and were randomized to treatment in Part A (66 participants) or Part B (119 participants). Overall results are presented per treatment arm
Participants by arm
| Arm | Count |
|---|---|
| Part A: EXPAREL 266 mg Arm subjects randomized to this treatment arm received 20 mL (266 mg) EXPAREL mixed with 10 mL saline
Bupivacaine liposome injectable suspension 266 mg: Sciatic nerve block in the popliteal fossa with EXPAREL 266 mg | 22 |
| Part A + B: EXPAREL 133 mg Arm subjects randomized to this treatment arm received 10 mL (133 mg) EXPAREL mixed with 20 mL saline
Bupivacaine liposome injectable suspension 133 mg: Sciatic nerve block in the popliteal fossa with EXPAREL 133 mg | 81 |
| Part A + B: Bupivacaine HCl Arm Subjects randomized to this treatment arm received 20 mL (50 mg) 0.25% bupivacaine HCl mixed with 10 mL saline
Bupivacaine HCl: Sciatic nerve block in the popliteal fossa with Bupivacaine HCl | 82 |
| Total | 185 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part A (14 Days) | Adverse Event | 1 | 0 | 0 |
| Part A (14 Days) | Failure to meet continuation criteria | 0 | 0 | 1 |
| Part A (14 Days) | Withdrawal by Subject | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Part A: EXPAREL 266 mg Arm | Part A + B: EXPAREL 133 mg Arm | Part A + B: Bupivacaine HCl Arm | Total |
|---|---|---|---|---|
| Age, Continuous | 48.36 years STANDARD_DEVIATION 10.896 | 50.15 years STANDARD_DEVIATION 12.823 | 47.24 years STANDARD_DEVIATION 11.95 | 48.65 years STANDARD_DEVIATION 12.239 |
| Age, Customized <45 Years | 6 Participants | 28 Participants | 30 Participants | 64 Participants |
| Age, Customized >=65 years | 0 Participants | 8 Participants | 5 Participants | 13 Participants |
| Age, Customized Between 45 and 65 years | 16 Participants | 45 Participants | 47 Participants | 108 Participants |
| ASA classification ASA 1 | 14 Participants | 39 Participants | 54 Participants | 107 Participants |
| ASA classification ASA 2 | 8 Participants | 42 Participants | 28 Participants | 78 Participants |
| Average pain intensity (NRS) | 3.9 units on a scale STANDARD_DEVIATION 2.23 | 3.4 units on a scale STANDARD_DEVIATION 2.1 | 3.8 units on a scale STANDARD_DEVIATION 2.33 | 3.7 units on a scale STANDARD_DEVIATION 2.22 |
| Body Mass Index <25 kg/m^2 | 8 Participants | 21 Participants | 24 Participants | 53 Participants |
| Body Mass Index 25 to <30 kg/m^2 | 10 Participants | 27 Participants | 32 Participants | 69 Participants |
| Body Mass Index ≥30 kg/m^2 | 4 Participants | 33 Participants | 26 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 26 Participants | 32 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 55 Participants | 50 Participants | 117 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 4 Participants | 25 Participants | 28 Participants | 57 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 9 Participants | 5 Participants | 16 Participants |
| Race/Ethnicity, Customized White | 16 Participants | 47 Participants | 49 Participants | 112 Participants |
| Region of Enrollment United States | 22 participants | 81 participants | 82 participants | 185 participants |
| Sex: Female, Male Female | 21 Participants | 74 Participants | 68 Participants | 163 Participants |
| Sex: Female, Male Male | 1 Participants | 7 Participants | 14 Participants | 22 Participants |
| Worst pain intensity (NRS) | 5.4 units on a scale STANDARD_DEVIATION 3 | 5.2 units on a scale STANDARD_DEVIATION 2.71 | 5.7 units on a scale STANDARD_DEVIATION 2.59 | 5.5 units on a scale STANDARD_DEVIATION 2.69 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 81 | 0 / 82 |
| other Total, other adverse events | 13 / 22 | 42 / 81 | 45 / 82 |
| serious Total, serious adverse events | 1 / 22 | 0 / 81 | 1 / 82 |
Outcome results
Primary
NRS Pain Scores Through 96 Hours Post-surgery
The numeric rating scale pain intensity scores ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 96 hours post-surgery. For each subject, the area under the curve was derived using the trapezoidal rule on the pain scores adjusted for opioid pain medication using the observed and imputed values. Area under the curve started with the first pain assessment obtained after surgery and use all subsequent pain assessments up to 96 hours post-surgery. Pain scores were taken at 5 interval point 0 hours, 24 hours, 48 hours, 72 hours, and 96 hours. There were also unscheduled pain scores measured before opioid consumption also included in the area under the curve calculation. The area under the curve ranged from 0 to 960. Higher scores represent a worse outcome.
Time frame: 0- 96 hours post-surgery
Population: The analysis was performed on the efficacy analysis set which included all participants in the safety analysis set who underwent the planned surgery and had at least one post-drug administration NRS pain assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: EXPAREL 266 mg Arm | NRS Pain Scores Through 96 Hours Post-surgery | 342.3 units on a scale*hours | Standard Deviation 265.35 |
| Part A + B: EXPAREL 133 mg Arm | NRS Pain Scores Through 96 Hours Post-surgery | 201.3 units on a scale*hours | Standard Deviation 180.05 |
| Part A + B: Bupivacaine HCl Arm | NRS Pain Scores Through 96 Hours Post-surgery | 377.4 units on a scale*hours | Standard Deviation 188.6 |
Comparison: The superiority of EXPAREL to bupivacaine hydrochloric acid (HCI) was evaluated using the Efficacy Analysis Set.p-value: <0.0000195% CI: [-218.3, -109.6]ANCOVA
Secondary
First Opioid Consumption Post-surgery
Time to first opioid consumption post-surgery
Time frame: 0 to 96 hours post-surgery
Population: The analysis was performed on the efficacy analysis set which included all participants in the safety analysis set who underwent the planned surgery and had at least one post-drug administration NRS pain assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: EXPAREL 266 mg Arm | First Opioid Consumption Post-surgery | 16.06 hours |
| Part A + B: EXPAREL 133 mg Arm | First Opioid Consumption Post-surgery | 20.27 hours |
| Part A + B: Bupivacaine HCl Arm | First Opioid Consumption Post-surgery | 20.68 hours |
p-value: 0.008995% CI: [0.45, 0.93]Cox proportional hazards model
Secondary
NRS Pain Scores Post-surgery
Worst and average NRS pain intensity scores at 24h, 48h, 72h, and 96h from the end of surgery Worst and average pain intensity scores on a numeric rating scale ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours. Mean scores at each timepoint are provided. The total range is 0 (no pain) to 10 (worst possible pain). Higher values on the scale represent worse outcome.
Time frame: 0-24 hours, 24-48 hours, 48-72 hours, and 72-96 hours post-surgery
Population: The number analyzed in one or more rows differs from overall number analyzed due to participant discontinuation from the study in Part A.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: EXPAREL 266 mg Arm | NRS Pain Scores Post-surgery | Average pain at 24 hours | 4.7 units on a scale | Standard Deviation 2.6 |
| Part A: EXPAREL 266 mg Arm | NRS Pain Scores Post-surgery | Worst pain at 24 hours | 6.0 units on a scale | Standard Deviation 3.18 |
| Part A: EXPAREL 266 mg Arm | NRS Pain Scores Post-surgery | Worst pain at 48 hours | 6.1 units on a scale | Standard Deviation 2.49 |
| Part A: EXPAREL 266 mg Arm | NRS Pain Scores Post-surgery | Worst pain at 96 hours | 4.4 units on a scale | Standard Deviation 3.68 |
| Part A: EXPAREL 266 mg Arm | NRS Pain Scores Post-surgery | Average pain at 72 hours | 3.5 units on a scale | Standard Deviation 3.19 |
| Part A: EXPAREL 266 mg Arm | NRS Pain Scores Post-surgery | Worst pain at 72 hours | 4.3 units on a scale | Standard Deviation 3.55 |
| Part A: EXPAREL 266 mg Arm | NRS Pain Scores Post-surgery | Average pain at 48 hours | 3.9 units on a scale | Standard Deviation 2.74 |
| Part A: EXPAREL 266 mg Arm | NRS Pain Scores Post-surgery | Average pain at 96 hours | 3.2 units on a scale | Standard Deviation 3.14 |
| Part A + B: EXPAREL 133 mg Arm | NRS Pain Scores Post-surgery | Average pain at 96 hours | 1.7 units on a scale | Standard Deviation 2.03 |
| Part A + B: EXPAREL 133 mg Arm | NRS Pain Scores Post-surgery | Worst pain at 72 hours | 2.7 units on a scale | Standard Deviation 2.87 |
| Part A + B: EXPAREL 133 mg Arm | NRS Pain Scores Post-surgery | Average pain at 72 hours | 1.8 units on a scale | Standard Deviation 2.05 |
| Part A + B: EXPAREL 133 mg Arm | NRS Pain Scores Post-surgery | Worst pain at 24 hours | 4.4 units on a scale | Standard Deviation 3.13 |
| Part A + B: EXPAREL 133 mg Arm | NRS Pain Scores Post-surgery | Worst pain at 48 hours | 4.4 units on a scale | Standard Deviation 3.14 |
| Part A + B: EXPAREL 133 mg Arm | NRS Pain Scores Post-surgery | Worst pain at 96 hours | 2.8 units on a scale | Standard Deviation 2.84 |
| Part A + B: EXPAREL 133 mg Arm | NRS Pain Scores Post-surgery | Average pain at 24 hours | 2.8 units on a scale | Standard Deviation 2.32 |
| Part A + B: EXPAREL 133 mg Arm | NRS Pain Scores Post-surgery | Average pain at 48 hours | 2.9 units on a scale | Standard Deviation 2.33 |
| Part A + B: Bupivacaine HCl Arm | NRS Pain Scores Post-surgery | Average pain at 72 hours | 4.1 units on a scale | Standard Deviation 2.19 |
| Part A + B: Bupivacaine HCl Arm | NRS Pain Scores Post-surgery | Worst pain at 96 hours | 5.1 units on a scale | Standard Deviation 2.81 |
| Part A + B: Bupivacaine HCl Arm | NRS Pain Scores Post-surgery | Average pain at 96 hours | 3.3 units on a scale | Standard Deviation 2.1 |
| Part A + B: Bupivacaine HCl Arm | NRS Pain Scores Post-surgery | Average pain at 48 hours | 4.8 units on a scale | Standard Deviation 2.01 |
| Part A + B: Bupivacaine HCl Arm | NRS Pain Scores Post-surgery | Average pain at 24 hours | 3.0 units on a scale | Standard Deviation 2.58 |
| Part A + B: Bupivacaine HCl Arm | NRS Pain Scores Post-surgery | Worst pain at 48 hours | 7.3 units on a scale | Standard Deviation 2.22 |
| Part A + B: Bupivacaine HCl Arm | NRS Pain Scores Post-surgery | Worst pain at 72 hours | 6.1 units on a scale | Standard Deviation 2.69 |
| Part A + B: Bupivacaine HCl Arm | NRS Pain Scores Post-surgery | Worst pain at 24 hours | 5.3 units on a scale | Standard Deviation 3.06 |
p-value: 0.029695% CI: [-1.7, 0]ANCOVA
p-value: <0.0000195% CI: [-3.6, -2.1]ANCOVA
p-value: <0.0000195% CI: [-4.1, -2.5]ANCOVA
p-value: <0.0000195% CI: [-3, -1.3]ANCOVA
p-value: 0.341995% CI: [-0.9, 0.6]ANCOVA
p-value: <0.0000195% CI: [-2.5, -1.3]ANCOVA
p-value: <0.0000195% CI: [-2.8, -1.6]ANCOVA
p-value: <0.0000195% CI: [-2.1, -0.9]ANCOVA
Secondary
Opioid-free Subjects Through 96 Hours Post-surgery
Percentage of opioid-free subjects through 96 hours
Time frame: 0 to 96 hours post-surgery
Population: The analysis was performed on the efficacy analysis set which included all participants in the safety analysis set who underwent the planned surgery and had at least one post-drug administration NRS pain assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: EXPAREL 266 mg Arm | Opioid-free Subjects Through 96 Hours Post-surgery | 4.5 percentage of participants |
| Part A + B: EXPAREL 133 mg Arm | Opioid-free Subjects Through 96 Hours Post-surgery | 33.3 percentage of participants |
| Part A + B: Bupivacaine HCl Arm | Opioid-free Subjects Through 96 Hours Post-surgery | 9.8 percentage of participants |
p-value: 0.000395% CI: [2.01, 12.62]ANCOVA
Secondary
Postsurgical Opioid Consumption Through 96 Hours Post-surgery
Total postsurgical opioid consumption in oral morphine equivalents (OMED) from 0 to 96 hours post-surgery
Time frame: 0 to 96 hours post-surgery
Population: The analysis was performed on the efficacy analysis set which included all participants in the safety analysis set who underwent the planned surgery and had at least one post-drug administration NRS pain assessment. Results presented for each treatment arm
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: EXPAREL 266 mg Arm | Postsurgical Opioid Consumption Through 96 Hours Post-surgery | 32.68 milligrams oral morphine equivalents | Geometric Coefficient of Variation 96.768 |
| Part A + B: EXPAREL 133 mg Arm | Postsurgical Opioid Consumption Through 96 Hours Post-surgery | 15.41 milligrams oral morphine equivalents | Geometric Coefficient of Variation 126.781 |
| Part A + B: Bupivacaine HCl Arm | Postsurgical Opioid Consumption Through 96 Hours Post-surgery | 41.62 milligrams oral morphine equivalents | Geometric Coefficient of Variation 83.925 |
Comparison: The superiority of EXPAREL to bupivacaine hydrochloric acid (HCI) was evaluated using the Efficacy Analysis Set.p-value: <0.0000195% CI: [0.28, 0.55]ANCOVA