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

Sponsor
Pacira Pharmaceuticals, Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT04518462
Collaborator
(none)
121
5
3
5.5
24.2
4.4

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

Study Type:
Interventional
Actual Enrollment :
121 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double Blinded, Active Controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of EXPAREL, EXPAREL Admixed With Bupivacaine HCl vs. Bupivacaine HCl Administered as Combined Sciatic (in Popliteal Fossa) and Saphenous (in Adductor Canal) Nerve Blocks for Postsurgical Analgesia in Subjects Undergoing Lower Extremity Surgeries
Actual Study Start Date :
Oct 20, 2020
Actual Primary Completion Date :
Apr 5, 2021
Actual Study Completion Date :
Apr 5, 2021

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

  1. 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

  1. Total Opioid Consumption [0 hours to 96 hours]

    Total Opioid Consumption in oral morphine equivalents

  2. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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)

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.
Responsible Party:
Pacira Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT04518462
Other Study ID Numbers:
  • 402-C-333
First Posted:
Aug 19, 2020
Last Update Posted:
Jul 18, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

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

1. Primary Outcome
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)
2. Secondary Outcome
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
3. Secondary Outcome
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

[Not Specified]

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
Email MedInfo@Pacira.com
Responsible Party:
Pacira Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT04518462
Other Study ID Numbers:
  • 402-C-333
First Posted:
Aug 19, 2020
Last Update Posted:
Jul 18, 2022
Last Verified:
Jul 1, 2022