STRIDE: Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of EXPAREL, EXPAREL Admixed With Bupivacaine HCl vs. Bupivacaine HCl Administered as Combined Sciatic and Saphenous Nerve Blocks for Postsurgical Analgesia in Subjects Undergoing Lower Extremity Surgeries
Study Details
Study Description
Brief Summary
This is a Phase 3, multicenter, randomized, double blinded, active controlled study in approximately 120 subjects undergoing lower extremity surgeries.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: EXPAREL arm Subjects randomized to this treatment arm will receive 20 mL (266 mg)EXPAREL mixed with 20 mL saline |
Drug: Exparel
EXPAREL (bupivacaine liposome injectable suspension)
|
Experimental: 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. |
Drug: Exparel
EXPAREL (bupivacaine liposome injectable suspension)
Drug: Bupivacaine Hydrochloride
0.25% bupivacaine
|
Active Comparator: Bupivacaine HCl Arm subjects randomized to this treatment arm will receive 40 mL (100 mg)0.25% bupivacaine HCl. |
Drug: Bupivacaine Hydrochloride
0.25% bupivacaine
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy adult male or female volunteers ages 18 or older
-
American Society of Anesthesiologists (ASA) physical status 1, 2, or 3
-
Able to provide informed consent, adhere to the study schedule, and complete all study assessments
-
Body Mass Index (BMI) ≥18 and ≤40 kg/m2
Exclusion Criteria:
-
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])
-
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
-
History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years
-
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
-
Previous participation in an EXPAREL study
-
Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the investigator, could interfere with study assessments or compliance
-
Currently pregnant, nursing, or planning to become pregnant during the study
-
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.
-
Currently on a neuromodulating agent neuroleptic agent (e.g., gabapentin, pregabalin [Lyrica], duloxetine [Cymbalta], etc.)
-
Inadequate sensory function on the foot (monofilament test)
-
Chronic opioid use within 30 days prior to randomization (average ≥30 oral morphine equivalents/day)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Arizona Research Center | Phoenix | Arizona | United States | 85053 |
2 | Lotus Clinical Research | Pasadena | California | United States | 91105 |
3 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
4 | Brigham and Women's Hospital | Chestnut Hill | Massachusetts | United States | 02467 |
5 | HD Research, Corp | Bellaire | Texas | United States | 77401 |
Sponsors and Collaborators
- Pacira Pharmaceuticals, Inc
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- 402-C-333
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | EXPAREL Arm | EXPAREL Admix Arm | Bupivacaine HCl Arm |
---|---|---|---|
Arm/Group Description | Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension) | 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 | subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine |
Period Title: Overall Study | |||
STARTED | 40 | 41 | 40 |
COMPLETED | 39 | 40 | 39 |
NOT COMPLETED | 1 | 1 | 1 |
Baseline Characteristics
Arm/Group Title | EXPAREL Arm | EXPAREL Admix Arm | Bupivacaine HCl Arm | Total |
---|---|---|---|---|
Arm/Group Description | Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension) | 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 | subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine | Total of all reporting groups |
Overall Participants | 39 | 40 | 40 | 119 |
Age, Customized (Count of Participants) | ||||
<45 years |
11
28.2%
|
14
35%
|
18
45%
|
43
36.1%
|
>/=45 years |
28
71.8%
|
26
65%
|
22
55%
|
76
63.9%
|
Sex: Female, Male (Count of Participants) | ||||
Female |
35
89.7%
|
36
90%
|
27
67.5%
|
98
82.4%
|
Male |
4
10.3%
|
4
10%
|
13
32.5%
|
21
17.6%
|
Ethnicity (NIH/OMB) (Count of Participants) | ||||
Hispanic or Latino |
10
25.6%
|
12
30%
|
15
37.5%
|
37
31.1%
|
Not Hispanic or Latino |
28
71.8%
|
26
65%
|
25
62.5%
|
79
66.4%
|
Unknown or Not Reported |
1
2.6%
|
2
5%
|
0
0%
|
3
2.5%
|
Race (NIH/OMB) (Count of Participants) | ||||
American Indian or Alaska Native |
0
0%
|
1
2.5%
|
0
0%
|
1
0.8%
|
Asian |
1
2.6%
|
0
0%
|
3
7.5%
|
4
3.4%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Black or African American |
5
12.8%
|
11
27.5%
|
7
17.5%
|
23
19.3%
|
White |
32
82.1%
|
26
65%
|
30
75%
|
88
73.9%
|
More than one race |
0
0%
|
1
2.5%
|
0
0%
|
1
0.8%
|
Unknown or Not Reported |
1
2.6%
|
1
2.5%
|
0
0%
|
2
1.7%
|
American Society of Anesthesiologists (ASA) Classification (Count of Participants) | ||||
ASA 1 |
15
38.5%
|
12
30%
|
23
57.5%
|
50
42%
|
ASA 2 |
24
61.5%
|
26
65%
|
17
42.5%
|
67
56.3%
|
ASA 3 |
0
0%
|
2
5%
|
0
0%
|
2
1.7%
|
ASA >/= 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Height (participants) [Number] | ||||
<165 cm |
20
51.3%
|
21
52.5%
|
20
50%
|
61
51.3%
|
>/= 165 cm |
19
48.7%
|
19
47.5%
|
20
50%
|
58
48.7%
|
Weight (kg) [Mean (Full Range) ] | ||||
Mean (Full Range) [kg] |
77.05
|
83.03
|
77.34
|
79.16
|
Body Mass Index (BMI) kg/m2 (participants) [Number] | ||||
<25 kg/m2 |
10
25.6%
|
9
22.5%
|
10
25%
|
29
24.4%
|
25- <30kg/m2 |
15
38.5%
|
10
25%
|
19
47.5%
|
44
37%
|
>/= 30 kg/m2 |
14
35.9%
|
21
52.5%
|
11
27.5%
|
46
38.7%
|
Average and worst pain intensity score (NRS) in the last 30 days (score on a scale) [Mean (Standard Deviation) ] | ||||
average NRS |
2.3
(2.53)
|
3.2
(2.94)
|
2.2
(2.24)
|
2.6
(2.60)
|
worst NRS |
3.3
(2.64)
|
4.5
(3.14)
|
3.3
(2.76)
|
3.7
(2.88)
|
Pain Catastrophizing Scale Total Score (score on a scale) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [score on a scale] |
11.7
(11.49)
|
13.4
(11.91)
|
11.0
(10.68)
|
12.0
(11.32)
|
Outcome Measures
Title | Magnitude of the Analgesic Effect (NRS Pain Intensity) (AUC) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | EXPAREL Arm | EXPAREL Admix Arm | Bupivacaine HCl Arm |
---|---|---|---|
Arm/Group Description | Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension) | 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 | subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine |
Measure Participants | 39 | 40 | 40 |
Mean (Standard Deviation) [score on a scale*hours] |
298.65
(173.524)
|
358.10
(223.610)
|
380.05
(220.878)
|
Title | Total Opioid Consumption |
---|---|
Description | Total Opioid Consumption in oral morphine equivalents |
Time Frame | 0 hours to 96 hours |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | EXPAREL Arm | EXPAREL Admix Arm | Bupivacaine HCl Arm |
---|---|---|---|
Arm/Group Description | Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension) | 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 | subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine |
Measure Participants | 39 | 40 | 40 |
Least Squares Mean (95% Confidence Interval) [OMED mg] |
20.68
|
23.56
|
19.84
|
Title | Time to First Opioid |
---|---|
Description | Time to First Opioid following a single dose of EXPAREL vs. Bupivacain HCl |
Time Frame | Post Surgery through Day 14 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | EXPAREL Arm | EXPAREL Admix Arm | Bupivacaine HCl Arm |
---|---|---|---|
Arm/Group Description | Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension) | 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 | subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine |
Measure Participants | 39 | 40 | 40 |
Mean (95% Confidence Interval) [hours] |
5.65
|
11.93
|
16.67
|
Adverse Events
Time Frame | Adverse events (AEs) and SAEs were recorded from the time of informed consent through POD 14. | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||
Arm/Group Title | EXPAREL Arm | EXPAREL Admix Arm | Bupivacaine HCl Arm | |||
Arm/Group Description | Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 20 mL saline EXPAREL (bupivacaine liposome injectable suspension) | 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 | subjects randomized to this treatment arm will receive 40 mL (100 mg) 0.25% bupivacaine HCl. Bupivacaine Hydrochloride: 0.25% bupivacaine | |||
All Cause Mortality |
||||||
EXPAREL Arm | EXPAREL Admix Arm | Bupivacaine HCl Arm | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/39 (0%) | 0/41 (0%) | 0/39 (0%) | |||
Serious Adverse Events |
||||||
EXPAREL Arm | EXPAREL Admix Arm | Bupivacaine HCl Arm | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/39 (0%) | 0/41 (0%) | 0/39 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
EXPAREL Arm | EXPAREL Admix Arm | Bupivacaine HCl Arm | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 28/39 (71.8%) | 29/41 (70.7%) | 31/39 (79.5%) | |||
Gastrointestinal disorders | ||||||
Constipation | 9/39 (23.1%) | 9 | 11/41 (26.8%) | 11 | 11/39 (28.2%) | 11 |
Nausea | 8/39 (20.5%) | 11 | 12/41 (29.3%) | 14 | 7/39 (17.9%) | 7 |
Vomiting | 1/39 (2.6%) | 3 | 6/41 (14.6%) | 8 | 2/39 (5.1%) | 2 |
General disorders | ||||||
Pyrexia | 2/39 (5.1%) | 2 | 0/41 (0%) | 0 | 1/39 (2.6%) | 1 |
Investigations | ||||||
Blood Pressure Increased | 2/39 (5.1%) | 2 | 2/41 (4.9%) | 2 | 1/39 (2.6%) | 1 |
Musculoskeletal and connective tissue disorders | ||||||
Pain in extremity | 2/39 (5.1%) | 2 | 0/41 (0%) | 0 | 1/39 (2.6%) | 1 |
Nervous system disorders | ||||||
Dizziness | 3/39 (7.7%) | 3 | 2/41 (4.9%) | 2 | 2/39 (5.1%) | 2 |
Headache | 10/39 (25.6%) | 10 | 4/41 (9.8%) | 5 | 7/39 (17.9%) | 7 |
Hypoaesthesia | 8/39 (20.5%) | 8 | 9/41 (22%) | 9 | 0/39 (0%) | 0 |
Motor dysfuction | 1/39 (2.6%) | 1 | 1/41 (2.4%) | 1 | 2/39 (5.1%) | 2 |
Paraesthesia | 5/39 (12.8%) | 8 | 3/41 (7.3%) | 6 | 11/39 (28.2%) | 12 |
Respiratory, thoracic and mediastinal disorders | ||||||
Cough | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 2/39 (5.1%) | 2 |
Epistaxis | 2/39 (5.1%) | 2 | 0/41 (0%) | 0 | 0/39 (0%) | 0 |
Hypoxia | 1/39 (2.6%) | 1 | 1/41 (2.4%) | 1 | 2/39 (5.1%) | 2 |
Skin and subcutaneous tissue disorders | ||||||
Pruritis | 3/39 (7.7%) | 3 | 1/41 (2.4%) | 1 | 1/39 (2.6%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results conducted at Site shall not be published before 1st multicenter publication by Sponsor but can proceed if there is no such publication </= 18 months after study completion/termination at all sites and all data have been received. Before submitting manuscript/materials to an outside person/entity, site shall give Sponsor 60 days to review and comment. Site shall, upon request, further delay publication/presentation for </=120 days to allow Sponsor to protect its interests in Inventions.
Results Point of Contact
Name/Title | Pacira Medical Information |
---|---|
Organization | Pacira Pharmaceuticals, Inc. |
Phone | 1-855-793-9729 |
MedInfo@Pacira.com |
- 402-C-333