Bunion, Hindfoot Fushion, Lower Extremity Surgery, Metatarsophalangeal Fushion, Midfoot Fusion, Total Ankle Arthroplasty
Conditions
Brief summary
This is a Phase 3, multicenter, randomized, double blinded, active controlled study in approximately 120 subjects undergoing lower extremity surgeries.
Interventions
DRUGExparel
EXPAREL (bupivacaine liposome injectable suspension)
DRUGBupivacaine Hydrochloride
0.25% bupivacaine
Sponsors
Pacira Pharmaceuticals, Inc
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 No maximum
Healthy volunteers
No
Inclusion criteria
1. Healthy adult male or female volunteers ages 18 or older 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. 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, nonsteroidal anti-inflammatory drugs \[NSAIDs\]) 2. Concurrent painful physical condition that may require analgesic treatment (such as long-term, consistent use of opioids) in the post dosing period for pain and which, in the investigator's opinion, may confound the post dosing assessments 3. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years 4. 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 5. Previous participation in an EXPAREL study 6. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the investigator, could interfere with study assessments or compliance 7. Currently pregnant, nursing, or planning to become pregnant during the study 8. 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. 9. Currently on a neuromodulating agent neuroleptic agent (e.g., gabapentin, pregabalin \[Lyrica\], duloxetine \[Cymbalta\], etc.) 10. Inadequate sensory function on the foot (monofilament test) 11. Chronic opioid use within 30 days prior to randomization (average ≥30 oral morphine equivalents/day)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Magnitude of the Analgesic Effect (NRS Pain Intensity) (AUC) | Post surgery - 96 hours | To compare the magnitude of the analgesic effect (NRS pain intensity scores) following a single dose injection of EXPAREL vs. bupivacaine hydrochloride (HCl) when administered as combined sciatic (in the popliteal fossa) and saphenous (in the adductor canal) nerve blocks in subjects undergoing lower extremity surgeries. Numerical Rating Scale: an 11 point scale 0=no pain, 10= the worst pain imaginable. The area under the curve (AUC) of the NRS pain intensity scores from 0 to 96 hours post-surgery comparing EXPAREL to 0.25% bupivacaine HCl |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Opioid Consumption | 0 hours to 96 hours | Total Opioid Consumption in oral morphine equivalents |
| Time to First Opioid | Post Surgery through Day 14 | Time to First Opioid following a single dose of EXPAREL vs. Bupivacain HCl |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EXPAREL Arm Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline
EXPAREL (bupivacaine liposome injectable suspension) | 39 |
| EXPAREL Admix Arm subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL admixed with 20 mL (50 mg) 0.25% bupivacaine HCl.
EXPAREL (bupivacaine liposome injectable suspension)
Bupivacaine Hydrochloride: 0.25% bupivacaine | 40 |
| Bupivacaine HCl Arm subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl.
Bupivacaine Hydrochloride: 0.25% bupivacaine | 40 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | EXPAREL Arm | EXPAREL Admix Arm | Bupivacaine HCl Arm | Total |
|---|---|---|---|---|
| Age, Customized <45 years | 11 Participants | 14 Participants | 18 Participants | 43 Participants |
| Age, Customized >/=45 years | 28 Participants | 26 Participants | 22 Participants | 76 Participants |
| American Society of Anesthesiologists (ASA) Classification ASA 1 | 15 Participants | 12 Participants | 23 Participants | 50 Participants |
| American Society of Anesthesiologists (ASA) Classification ASA 2 | 24 Participants | 26 Participants | 17 Participants | 67 Participants |
| American Society of Anesthesiologists (ASA) Classification ASA 3 | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| American Society of Anesthesiologists (ASA) Classification ASA >/= 4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Average and worst pain intensity score (NRS) in the last 30 days average NRS | 2.3 score on a scale STANDARD_DEVIATION 2.53 | 3.2 score on a scale STANDARD_DEVIATION 2.94 | 2.2 score on a scale STANDARD_DEVIATION 2.24 | 2.6 score on a scale STANDARD_DEVIATION 2.6 |
| Average and worst pain intensity score (NRS) in the last 30 days worst NRS | 3.3 score on a scale STANDARD_DEVIATION 2.64 | 4.5 score on a scale STANDARD_DEVIATION 3.14 | 3.3 score on a scale STANDARD_DEVIATION 2.76 | 3.7 score on a scale STANDARD_DEVIATION 2.88 |
| Body Mass Index (BMI) kg/m2 25- <30kg/m2 | 15 participants | 10 participants | 19 participants | 44 participants |
| Body Mass Index (BMI) kg/m2 <25 kg/m2 | 10 participants | 9 participants | 10 participants | 29 participants |
| Body Mass Index (BMI) kg/m2 >/= 30 kg/m2 | 14 participants | 21 participants | 11 participants | 46 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 12 Participants | 15 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 26 Participants | 25 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Height <165 cm | 20 participants | 21 participants | 20 participants | 61 participants |
| Height >/= 165 cm | 19 participants | 19 participants | 20 participants | 58 participants |
| Pain Catastrophizing Scale Total Score | 11.7 score on a scale STANDARD_DEVIATION 11.49 | 13.4 score on a scale STANDARD_DEVIATION 11.91 | 11.0 score on a scale STANDARD_DEVIATION 10.68 | 12.0 score on a scale STANDARD_DEVIATION 11.32 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 11 Participants | 7 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 32 Participants | 26 Participants | 30 Participants | 88 Participants |
| Sex: Female, Male Female | 35 Participants | 36 Participants | 27 Participants | 98 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 13 Participants | 21 Participants |
| Weight | 77.05 kg | 83.03 kg | 77.34 kg | 79.16 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 41 | 0 / 39 |
| other Total, other adverse events | 28 / 39 | 29 / 41 | 31 / 39 |
| serious Total, serious adverse events | 0 / 39 | 0 / 41 | 0 / 39 |
Outcome results
Primary
Magnitude of the Analgesic Effect (NRS Pain Intensity) (AUC)
To compare the magnitude of the analgesic effect (NRS pain intensity scores) following a single dose injection of EXPAREL vs. bupivacaine hydrochloride (HCl) when administered as combined sciatic (in the popliteal fossa) and saphenous (in the adductor canal) nerve blocks in subjects undergoing lower extremity surgeries. Numerical Rating Scale: an 11 point scale 0=no pain, 10= the worst pain imaginable. The area under the curve (AUC) of the NRS pain intensity scores from 0 to 96 hours post-surgery comparing EXPAREL to 0.25% bupivacaine HCl
Time frame: Post surgery - 96 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EXPAREL Arm | Magnitude of the Analgesic Effect (NRS Pain Intensity) (AUC) | 298.65 score on a scale*hours | Standard Deviation 173.524 |
| EXPAREL Admix Arm | Magnitude of the Analgesic Effect (NRS Pain Intensity) (AUC) | 358.10 score on a scale*hours | Standard Deviation 223.61 |
| Bupivacaine HCl Arm | Magnitude of the Analgesic Effect (NRS Pain Intensity) (AUC) | 380.05 score on a scale*hours | Standard Deviation 220.878 |
Secondary
Time to First Opioid
Time to First Opioid following a single dose of EXPAREL vs. Bupivacain HCl
Time frame: Post Surgery through Day 14
| Arm | Measure | Value (MEAN) |
|---|---|---|
| EXPAREL Arm | Time to First Opioid | 5.65 hours |
| EXPAREL Admix Arm | Time to First Opioid | 11.93 hours |
| Bupivacaine HCl Arm | Time to First Opioid | 16.67 hours |
Secondary
Total Opioid Consumption
Total Opioid Consumption in oral morphine equivalents
Time frame: 0 hours to 96 hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| EXPAREL Arm | Total Opioid Consumption | 20.68 OMED mg |
| EXPAREL Admix Arm | Total Opioid Consumption | 23.56 OMED mg |
| Bupivacaine HCl Arm | Total Opioid Consumption | 19.84 OMED mg |