Femoral Nerve Block With Liposome Bupivacaine for Postsurgical Analgesia Following Total Knee Arthroplasty
Sponsor
Pacira Pharmaceuticals, Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT01683071
Collaborator
(none)
297
30
6
15
9.9
0.7
Study Details
Study Description
Brief Summary
The primary objectives of Part 1 are to (1) evaluate three dose levels of liposome bupivacaine versus placebo with respect to the magnitude and duration of the analgesic effect achieved following single dose injection femoral nerve block with liposome bupivacaine, and (2) select a single therapeutic dose of liposome bupivacaine from the three dose levels to be tested in Part 2.
Part 2: The primary objective of Part 2 is to compare the magnitude and duration of the analgesic effect of single injection femoral nerve block of a single dose level of liposome bupivacaine (selected from Part 1) with placebo (preservative-free normal saline).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
This is a Phase 2/3, multicenter, randomized, double-blind, parallel-group, placebo-controlled, dose-ranging study in subjects undergoing primary unilateral total knee arthroplasty (TKA) under general or spinal anesthesia. Note: Bupivacaine cannot be used as the spinal anesthetic.
Part 1 During Part 1 of the study, approximately 100 subjects (25 per treatment arm) will be randomized to receive a single dose injection femoral nerve block with either one of three doses of liposome bupivacaine (67, 133, or 266 mg) or placebo in 20 mL under ultrasound guidance. Preservative-free normal saline will be added to the 67 mg and 133 mg doses of study drug to achieve a volume of 20 mL.
Part 2 In Part 2 of the study, approximately 180 subjects (randomized 1:1, resulting in approximately 90 liposome bupivacaine subjects and 90 placebo subjects) will receive a single dose injection femoral nerve block with the selected dose level of liposome bupivacaine (i.e., 67, 133, or 266 mg) or placebo in 20 mL under ultrasound guidance.
Study Design
Study Type:
Interventional
Actual Enrollment
:
297 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Dose Ranging Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Single Injection Femoral Nerve Block With Liposome Bupivacaine for Postsurgical Analgesia in Subjects Undergoing Total Knee Arthroplasty
Study Start Date
:
Sep 1, 2012
Actual Primary Completion Date
:
Dec 1, 2013
Actual Study Completion Date
:
Dec 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: (Part 1) EXPAREL 67 mg 5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively |
Drug: EXPAREL 67 mg
5 mL EXPAREL expanded with 15 mL normal saline as single-injection femoral nerve block prior to total knee arthroplasty
Other Names:
|
| Experimental: (Part 1) EXPAREL 133 mg 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively |
Drug: EXPAREL 133 mg
10 mL EXPAREL expanded with 10 mL normal saline as single-injection femoral nerve block prior to total knee arthroplasty
Other Names:
|
| Experimental: (Part 1) EXPAREL 266 mg 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively |
Drug: EXPAREL 266 mg
20 mL EXPAREL as single-injection femoral nerve block prior to total knee arthroplasty
Other Names:
|
| Placebo Comparator: (Part 1) Placebo 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively |
Drug: Placebo
Normal saline 20 mL as single-injection femoral nerve block prior to total knee arthroplasty
Other Names:
|
| Experimental: (Part 2) EXPAREL 266 mg 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively |
Drug: EXPAREL 266 mg
20 mL EXPAREL as single-injection femoral nerve block prior to total knee arthroplasty
Other Names:
|
| Placebo Comparator: (Part 2) Placebo 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively |
Drug: Placebo
Normal saline 20 mL as single-injection femoral nerve block prior to total knee arthroplasty
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Area Under the Curve (AUC) of Numeric Rating Scale at Rest (NRS-R) Pain Intensity Scores Through 72 Hours [0-72 hours]
AUC of NRS-R pain intensity scores through 72 hours. Pain intensity scores were measured on an 11-point NRS (0=no pain and 10=worst possible pain)
Secondary Outcome Measures
- Total Postsurgical Opioid Consumption Through 72 Hours [0-72 hours]
Total postsurgical opioid consumption of opioid rescue pain medication (converted to IV morphine equivalents) through 72 hours
- Time to First Opioid Rescue Through 72 Hours [0-72 hours]
Time to first opioid rescue medication consumed through 72 hours
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female, >=18 years of age.
-
Scheduled to undergo primary unilateral TKA under general or spinal anesthesia.
-
American Society of Anesthesiologists (ASA) Physical Status 1, 2, or 3.
-
Able to demonstrate motor function by performing a 20-meter walk, unassisted with the optional use of a 4-legged walker, and sensory function by exhibiting sensitivity to cold.
-
Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.
Exclusion Criteria:
- Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration. Female subjects must be surgically sterile, at least 2 years menopausal, or using an acceptable method of birth control.
If of childbearing potential, must have a documented negative pregnancy test within 24 hours before surgery.
-
Planned concurrent surgical procedure (e.g., bilateral TKA).
-
Use of any of the following medications within the times specified before surgery:
long-acting opioid medication, NSAIDs, aspirin (except for low-dose aspirin used for cardioprotection) or acetaminophen within 3 days, or and any opioid medication within 24 hours.
-
Concurrent painful physical condition or concurrent surgery that may require analgesic treatment (such as an NSAID or opioid) in the postsurgical period for pain that is not strictly related to the surgical site administered study treatment, and which may confound the postsurgical assessments (e.g., significant pain from other joints including the non-index knee joint, chronic neuropathic pain, prior contralateral TKA, concurrent foot surgery).
-
Initiation of treatment with any of the following medications within 1 month of study drug administration or if the medication(s) are being given to control pain: selective serotonin reuptake inhibitors (SSRIs), selective norepinepherine reuptake inhibitors (SNRIs), gabapentin, pregabalin (Lyrica®), or duloxetine (Cymbalta®).
-
Current use of systemic glucocorticosteroids within 1 month of enrollment in this study.
-
Body weight < 50 kilograms (110 pounds) or a body mass index ≥ 40 kg/m2.
-
Contraindication to hydromorphone, oxycodone, or bupivacaine.
-
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 a liposome bupivacaine study.
-
History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
-
Failure to pass the urine drug screen.
-
Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, could interfere with study assessments or compliance.
-
Malignancy in the last 2 years, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
-
Current or historical evidence of any clinically significant disease or condition, especially cardiovascular or neurological conditions that, in the opinion of the Investigator, may increase the risk of surgery or complicate the subject's postsurgical course.
-
Significant medical conditions or laboratory results that, in the opinion of the Investigator, indicate an increased vulnerability to study drugs and procedures.
-
Subjects who are planned to receive Entereg® (alvimopan).
-
Subjects who will receive prophylactic antiemetics or planned postsurgical antiemetics given without regard to the subject's emesis needs.
-
Use of dexmedetomidine HCl (Precedex®) within 3 days of surgery.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ACHIEVE CLINICAL RESEARCH LLC 2017 Canyon Road Suite 41 | Birmingham | Alabama | United States | 35216 |
| 2 | HORIZON RESEARCH GROUP INC 3610 Springhill Memorial Dr. N | Mobile | Alabama | United States | 36608 |
| 3 | Veritas Research, LLC | Mobile | Alabama | United States | 36660 |
| 4 | SHOALS MEDICAL TRIALS INC. 1300 S Montgomery Ave | Sheffield | Alabama | United States | 35660 |
| 5 | PHOENIX ORTHOPAEDIC SURGEONS 2525 W. Greenway Road Suite 114 | Phoenix | Arizona | United States | 85023 |
| 6 | ALLIANCE RESEARCH CENTERS 24411 Health Center Drive Suite 350 | Laguna Hills | California | United States | 92653 |
| 7 | ORTHOPADIC SURGERY Loma Linda University Health Care Dept. Pf Orthopaedic Surgery 250 East Caroline Street Suite A | San Bernardino | California | United States | 92508 |
| 8 | University of California, San Diego | San Diego | California | United States | 92103 |
| 9 | Ilfeld, Brian (Thornton) UNIVERSITY OF CALIFORNIA, SAN DIEGO 10610 Hunters Glen Drive | San Diego | California | United States | 92130 |
| 10 | FLORIDA RESEARCH ASSOCIATES, LLC / FLORIDA ORTHOPAEDIC ASSOCIATES 740 W. Plymouth Ave | DeLand | Florida | United States | 32720 |
| 11 | JACKSON MEMORIAL HOSPITAL UNVERSITY OF MIAMI 1611 Nw. 12th Ave C300 | Miami | Florida | United States | 33136 |
| 12 | PENSACOLA RESEARCH CONSULTANTS,INC 5149 N.9th Avenue Suite 241 | Pensacola | Florida | United States | 32504 |
| 13 | SHERIDAN CLINICAL RESEARCH, INC. 1613 N. Harrison Parkway Building C Suite 200 | Sunrise | Florida | United States | 33323 |
| 14 | PHOENIX CLINICAL RESEARCH,LLC 7171 N. University Drive Suite 100 | Tamarac | Florida | United States | 33321 |
| 15 | UNIVERSITY OF KANSAS HOSPITAL & MEDICAL CENTER Dept. Of Anesthesiology 3901 Rainbow Blvd. Ms 1034 | Kansas City | Kansas | United States | 66160 |
| 16 | BEAUMONT HEALTH SYSTEM 44201 Dequindre Road Suite Pob 120 | Troy | Michigan | United States | 48085 |
| 17 | COOPER UNIVERSITY HOSPITAL 1 Cooper Plaza 202 Dorrance Building | Camden | New Jersey | United States | 08103 |
| 18 | UNIVERSITY OF MEDICINE AND DENSITRY OF NEW JERSEY/NEW JERSEY MEDICAL SCHOOL 185 South Orange Ave. Department of Anesthesiology - MSB E538 | Newark | New Jersey | United States | 07101 |
| 19 | NORTHERN WESTCHESTER HOSPTIAL Department Of Clinical Trials 400 East Main St. | Mount Kisco | New York | United States | 10549 |
| 20 | ST. LUKE-ROOSEVELT HOSPITAL CENTER Dept. Of Anesthesiology 1111 Amsterdam Ave. Travis Bld. 7 | New York | New York | United States | 10025 |
| 21 | INSALL-SCOTT-KELLY INSTITUTE 210 East 64th Street | New York | New York | United States | 10065 |
| 22 | UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL Department Of Anesthesiology 101 Manning Drive N0021, Cb 7010 | Chapel Hill | North Carolina | United States | 27599 |
| 23 | CLEVELAND CLINIC FAIRVIEW HOSPTIAL 1801 Lorain Avenue | Cleveland | Ohio | United States | 44111 |
| 24 | CLEVELAND CLINIC 9500 Euclid Ave P-77 | Cleveland | Ohio | United States | 44195 |
| 25 | PENN STATE MILTON S. HERSHEY MEDICAL CENTER H187,500 University Drive | Hershey | Pennsylvania | United States | 17033 |
| 26 | THOMAS JEFFERSON UNIVERSITY Dept. Of Anesthesiology 111 S. 11th Street Suite G 8490 | Philadelphia | Pennsylvania | United States | 19107 |
| 27 | UPMC PRESBYTERIAN SHADYSIDE/ DEPT. OF ANESTHESIOLOGY POSNER PAIN CENTER 532 South Aiken Avenue Suite 407 | Pittsburgh | Pennsylvania | United States | 15232 |
| 28 | UNIVERSITY OF TEXAS MEDICAL BRANCH Dept. Chairman, Orthopedic Surgery & Rehabilitation 2.316 Rebecca Sealy Hospital 301 University Blvd. | Galveston | Texas | United States | 77551 |
| 29 | RESEARCH CONCEPTS,GP LLC 921 Gessner Rd. Anesthesia Dept., Classroom F | Houston | Texas | United States | 77024 |
| 30 | CHRISTUS ST. JOHN HOSPITAL 18300 St. John Dr., 2nd Floor, Surgery | Nassau Bay | Texas | United States | 77058 |
Sponsors and Collaborators
- Pacira Pharmaceuticals, Inc
Investigators
- Study Director: Erol Onel, MD, Pacira Pharmaceuticals, Inc
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Pacira Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01683071
Other Study ID Numbers:
- 402-C-323
First Posted:
Sep 11, 2012
Last Update Posted:
Dec 9, 2020
Last Verified:
Nov 1, 2020
Keywords provided by Pacira Pharmaceuticals, Inc
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were recruited between September 24, 2012 and December 20, 2013 at 23 sites in the US |
|---|---|
| Pre-assignment Detail | An unblinded dose selection committee reviewed Part 1 results for the primary endpoint, total postsurgical opioid consumption, time to first opioid rescue, and safety data, and recommended a dose level and sample size for Part 2. |
| Arm/Group Title | (Part 1) EXPAREL 67 mg | (Part 1) EXPAREL 133 mg | (Part 1) EXPAREL 266 mg | (Part 1) Placebo | (Part 2) EXPAREL 266 mg | (Part 2) Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | 5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively |
| Period Title: Part 1 | ||||||
| STARTED | 25 | 26 | 25 | 25 | 0 | 0 |
| COMPLETED | 21 | 22 | 22 | 20 | 0 | 0 |
| NOT COMPLETED | 4 | 4 | 3 | 5 | 0 | 0 |
| Period Title: Part 1 | ||||||
| STARTED | 0 | 0 | 0 | 0 | 99 | 97 |
| COMPLETED | 0 | 0 | 0 | 0 | 82 | 82 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 17 | 15 |
Baseline Characteristics
| Arm/Group Title | (Part 1) EXPAREL 67 mg | (Part 1) EXPAREL 133 mg | (Part 1) EXPAREL 266 mg | (Part 1) Placebo | (Part 2) EXPAREL 266 mg | (Part 2) Placebo | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | Total of all reporting groups |
| Overall Participants | 22 | 24 | 24 | 24 | 92 | 92 | 278 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
68.5
(8.41)
|
65.7
(7.30)
|
66.4
(8.94)
|
66.1
(12.17)
|
66.4
(10.35)
|
63.6
(8.76)
|
65.0
(9.67)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
8
36.4%
|
16
66.7%
|
14
58.3%
|
14
58.3%
|
52
56.5%
|
57
62%
|
161
57.9%
|
| Male |
14
63.6%
|
8
33.3%
|
10
41.7%
|
10
41.7%
|
40
43.5%
|
35
38%
|
117
42.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||
| Hispanic or Latino |
1
4.5%
|
1
4.2%
|
2
8.3%
|
3
12.5%
|
8
8.7%
|
9
9.8%
|
24
8.6%
|
| Not Hispanic or Latino |
21
95.5%
|
23
95.8%
|
22
91.7%
|
21
87.5%
|
84
91.3%
|
83
90.2%
|
254
91.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.1%
|
1
0.4%
|
| Asian |
1
4.5%
|
0
0%
|
1
4.2%
|
0
0%
|
2
2.2%
|
0
0%
|
4
1.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
4.5%
|
2
8.3%
|
2
8.3%
|
4
16.7%
|
15
16.3%
|
14
15.2%
|
38
13.7%
|
| White |
20
90.9%
|
22
91.7%
|
21
87.5%
|
20
83.3%
|
75
81.5%
|
76
82.6%
|
234
84.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.1%
|
1
0.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||||||
| United States |
22
100%
|
24
100%
|
24
100%
|
24
100%
|
92
100%
|
92
100%
|
278
100%
|
| American Society of Anesthesiologists (ASA) classification (Count of Participants) | |||||||
| 1 |
0
0%
|
0
0%
|
1
4.2%
|
0
0%
|
7
7.6%
|
3
3.3%
|
11
4%
|
| 2 |
11
50%
|
16
66.7%
|
13
54.2%
|
15
62.5%
|
38
41.3%
|
49
53.3%
|
142
51.1%
|
| 3 |
11
50%
|
8
33.3%
|
10
41.7%
|
9
37.5%
|
47
51.1%
|
40
43.5%
|
125
45%
|
| >/= 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Type of Anesthesia (Count of Participants) | |||||||
| General |
15
68.2%
|
17
70.8%
|
12
50%
|
21
87.5%
|
62
67.4%
|
56
60.9%
|
183
65.8%
|
| Spinal |
6
27.3%
|
7
29.2%
|
12
50%
|
3
12.5%
|
28
30.4%
|
35
38%
|
91
32.7%
|
| Other |
1
4.5%
|
0
0%
|
0
0%
|
0
0%
|
2
2.2%
|
0
0%
|
3
1.1%
|
| Duration of Surgery (minutes) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [minutes] |
85.8
(25.53)
|
88.5
(27.96)
|
96.0
(37.94)
|
85.0
(35.53)
|
94.1
(34.43)
|
94.9
(37.54)
|
94.5
(35.9)
|
| Incision length (cm) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [cm] |
16.51
(2.457)
|
14.98
(3.650)
|
15.23
(2.834)
|
18.25
(3.870)
|
16.92
(4.987)
|
16.29
(5.189)
|
16.6
(5.08)
|
Outcome Measures
| Title | Area Under the Curve (AUC) of Numeric Rating Scale at Rest (NRS-R) Pain Intensity Scores Through 72 Hours |
|---|---|
| Description | AUC of NRS-R pain intensity scores through 72 hours. Pain intensity scores were measured on an 11-point NRS (0=no pain and 10=worst possible pain) |
| Time Frame | 0-72 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy population: all participants in the safety analysis set who underwent the planned surgery, with analysis based on randomized treatment (regardless of treatment received) |
| Arm/Group Title | (Part 1) EXPAREL 67 mg | (Part 1) EXPAREL 133 mg | (Part 1) EXPAREL 266 mg | (Part 1) Placebo | (Part 2) EXPAREL 266 mg | (Part 2) Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | 5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively EXPAREL: EXPAREL 67 mg, 133 mg, or 266 mg | 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively EXPAREL: EXPAREL 67 mg, 133 mg, or 266 mg | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively EXPAREL: EXPAREL 67 mg, 133 mg, or 266 mg | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively Placebo: Normal saline 20 mL | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively EXPAREL: EXPAREL 67 mg, 133 mg, or 266 mg | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively Placebo: Normal saline 20 mL |
| Measure Participants | 22 | 24 | 24 | 24 | 92 | 91 |
| Least Squares Mean (Standard Deviation) [score on a scale * hr] |
533.4
(33.15)
|
427.2
(31.73)
|
436.2
(31.79)
|
530.5
(31.73)
|
418.9
(16.86)
|
515.5
(16.95)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | (Part 1) EXPAREL 67 mg, (Part 1) Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9494 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSMD |
| Estimated Value | 2.9 | |
| Confidence Interval |
(2-Sided) 95% -88 to 94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | (Part 1) EXPAREL 133 mg, (Part 1) Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0237 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSMD |
| Estimated Value | -103.3 | |
| Confidence Interval |
(2-Sided) 95% -192 to -14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | (Part 1) EXPAREL 266 mg, (Part 1) Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0386 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSMD |
| Estimated Value | -94.3 | |
| Confidence Interval |
(2-Sided) 95% -184 to -5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | (Part 2) EXPAREL 266 mg, (Part 2) Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSMD |
| Estimated Value | -96.5 | |
| Confidence Interval |
(2-Sided) 95% -144 to -49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Total Postsurgical Opioid Consumption Through 72 Hours |
|---|---|
| Description | Total postsurgical opioid consumption of opioid rescue pain medication (converted to IV morphine equivalents) through 72 hours |
| Time Frame | 0-72 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy population: all participants in the safety analysis set who underwent the planned surgery, with analysis based on randomized treatment (regardless of treatment received) |
| Arm/Group Title | (Part 1) EXPAREL 67 mg | (Part 1) EXPAREL 133 mg | (Part 1) EXPAREL 266 mg | (Part 1) Placebo | (Part 2) EXPAREL 266 mg | (Part 2) Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | 5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively |
| Measure Participants | 22 | 24 | 24 | 24 | 92 | 91 |
| Mean (Standard Deviation) [mg morphine equivalents] |
126.69
(75.972)
|
100.35
(53.177)
|
105.96
(53.402)
|
124.78
(58.743)
|
93.19
(58.133)
|
122.08
(70.312)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | (Part 1) EXPAREL 67 mg, (Part 1) Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6182 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric LSM ratio |
| Estimated Value | 0.90 | |
| Confidence Interval |
(2-Sided) 95% 0.6 to 1.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | (Part 1) EXPAREL 133 mg, (Part 1) Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1097 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric LSM ratio |
| Estimated Value | 0.73 | |
| Confidence Interval |
(2-Sided) 95% 0.5 to 1.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | (Part 1) EXPAREL 266 mg, (Part 1) Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4046 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric LSM ratio |
| Estimated Value | 0.85 | |
| Confidence Interval |
(2-Sided) 95% 0.6 to 1.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | (Part 2) EXPAREL 266 mg, (Part 2) Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0016 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric LSM ratio |
| Estimated Value | 0.74 | |
| Confidence Interval |
(2-Sided) 95% 0.6 to 0.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to First Opioid Rescue Through 72 Hours |
|---|---|
| Description | Time to first opioid rescue medication consumed through 72 hours |
| Time Frame | 0-72 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy population: all participants in the safety analysis set who underwent the planned surgery, with analysis based on randomized treatment (regardless of treatment received) |
| Arm/Group Title | (Part 1) EXPAREL 67 mg | (Part 1) EXPAREL 133 mg | (Part 1) EXPAREL 266 mg | (Part 1) Placebo | (Part 2) EXPAREL 266 mg | (Part 2) Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | 5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively |
| Measure Participants | 22 | 24 | 24 | 24 | 92 | 91 |
| Median (95% Confidence Interval) [hours] |
0.49
|
0.37
|
1.29
|
0.41
|
0.44
|
0.43
|
Adverse Events
| Time Frame | From screening through postsurgical day 30 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov. The safety analysis set includes all subjects who received study drug, based on treatment received. | |||||||||||
| Arm/Group Title | (Part 1) EXPAREL 67 mg | (Part 1) EXPAREL 133 mg | (Part 1) EXPAREL 266 mg | (Part 1) Placebo | (Part 2) EXPAREL 266 mg | (Part 2) Placebo | ||||||
| Arm/Group Description | 5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively | ||||||
All Cause Mortality |
||||||||||||
| (Part 1) EXPAREL 67 mg | (Part 1) EXPAREL 133 mg | (Part 1) EXPAREL 266 mg | (Part 1) Placebo | (Part 2) EXPAREL 266 mg | (Part 2) Placebo | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 0/92 (0%) | 0/92 (0%) | ||||||
Serious Adverse Events |
||||||||||||
| (Part 1) EXPAREL 67 mg | (Part 1) EXPAREL 133 mg | (Part 1) EXPAREL 266 mg | (Part 1) Placebo | (Part 2) EXPAREL 266 mg | (Part 2) Placebo | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/22 (18.2%) | 2/24 (8.3%) | 1/24 (4.2%) | 3/24 (12.5%) | 8/92 (8.7%) | 9/92 (9.8%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anemia | 2/22 (9.1%) | 0/24 (0%) | 1/24 (4.2%) | 0/24 (0%) | 1/92 (1.1%) | 2/92 (2.2%) | ||||||
| Cardiac disorders | ||||||||||||
| Cardiac Failure Congestive | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 1/92 (1.1%) | 0/92 (0%) | ||||||
| Myocardial Infarction | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 1/92 (1.1%) | 0/92 (0%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| ileus | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 1/92 (1.1%) | 1/92 (1.1%) | ||||||
| General disorders | ||||||||||||
| Local Swelling | 0/22 (0%) | 1/24 (4.2%) | 0/24 (0%) | 0/24 (0%) | 0/92 (0%) | 0/92 (0%) | ||||||
| Pyrexia | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 4/92 (4.3%) | 1/92 (1.1%) | ||||||
| Edema | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 1/92 (1.1%) | 0/92 (0%) | ||||||
| Systemic Inflammatory Response Syndrome | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 0/92 (0%) | 1/92 (1.1%) | ||||||
| Immune system disorders | ||||||||||||
| Type IV Hypersensitivity Reaction | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 0/92 (0%) | 1/92 (1.1%) | ||||||
| Infections and infestations | ||||||||||||
| Cellulitis | 1/22 (4.5%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 0/92 (0%) | 0/92 (0%) | ||||||
| Device Related Infection | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 1/24 (4.2%) | 0/92 (0%) | 0/92 (0%) | ||||||
| Wound Infection | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 1/24 (4.2%) | 0/92 (0%) | 1/92 (1.1%) | ||||||
| Pneumonia | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 1/92 (1.1%) | 1/92 (1.1%) | ||||||
| Urinary Tract Infection | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 2/92 (2.2%) | 0/92 (0%) | ||||||
| Injury, poisoning and procedural complications | ||||||||||||
| Wound Dehiscence | 1/22 (4.5%) | 0/24 (0%) | 0/24 (0%) | 1/24 (4.2%) | 0/92 (0%) | 0/92 (0%) | ||||||
| Wound Decomposition | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 1/24 (4.2%) | 0/92 (0%) | 0/92 (0%) | ||||||
| Wound Necrosis | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 1/24 (4.2%) | 0/92 (0%) | 0/92 (0%) | ||||||
| Investigations | ||||||||||||
| Liver function test abnormal | 1/22 (4.5%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 0/92 (0%) | 0/92 (0%) | ||||||
| Metabolism and nutrition disorders | ||||||||||||
| Hypokalemia | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 1/92 (1.1%) | 0/92 (0%) | ||||||
| Hypovolemia | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 0/92 (0%) | 1/92 (1.1%) | ||||||
| Nervous system disorders | ||||||||||||
| Syncope | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 1/24 (4.2%) | 0/92 (0%) | 1/92 (1.1%) | ||||||
| Renal and urinary disorders | ||||||||||||
| Acute Prerenal Failure | 1/22 (4.5%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 0/92 (0%) | 0/92 (0%) | ||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Hypoxia | 0/22 (0%) | 1/24 (4.2%) | 0/24 (0%) | 0/24 (0%) | 0/92 (0%) | 0/92 (0%) | ||||||
| Pulmonary Congestion | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 0/92 (0%) | 1/92 (1.1%) | ||||||
| Vascular disorders | ||||||||||||
| Deep Vein Thrombosis | 1/22 (4.5%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 0/92 (0%) | 0/92 (0%) | ||||||
| Orthostatic Hypotension | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 1/92 (1.1%) | 1/92 (1.1%) | ||||||
Other (Not Including Serious) Adverse Events |
||||||||||||
| (Part 1) EXPAREL 67 mg | (Part 1) EXPAREL 133 mg | (Part 1) EXPAREL 266 mg | (Part 1) Placebo | (Part 2) EXPAREL 266 mg | (Part 2) Placebo | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/22 (86.4%) | 20/24 (83.3%) | 21/24 (87.5%) | 21/24 (87.5%) | 82/92 (89.1%) | 83/92 (90.2%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 4/22 (18.2%) | 1/24 (4.2%) | 4/24 (16.7%) | 2/24 (8.3%) | 8/92 (8.7%) | 5/92 (5.4%) | ||||||
| Cardiac disorders | ||||||||||||
| Tachycardia | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 5/92 (5.4%) | 6/92 (6.5%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Nausea | 8/22 (36.4%) | 14/24 (58.3%) | 13/24 (54.2%) | 9/24 (37.5%) | 49/92 (53.3%) | 61/92 (66.3%) | ||||||
| Constipation | 3/22 (13.6%) | 2/24 (8.3%) | 6/24 (25%) | 1/24 (4.2%) | 32/92 (34.8%) | 32/92 (34.8%) | ||||||
| Vomiting | 1/22 (4.5%) | 0/24 (0%) | 1/24 (4.2%) | 2/24 (8.3%) | 26/92 (28.3%) | 38/92 (41.3%) | ||||||
| General disorders | ||||||||||||
| Pyrexia | 8/22 (36.4%) | 7/24 (29.2%) | 8/24 (33.3%) | 3/24 (12.5%) | 28/92 (30.4%) | 24/92 (26.1%) | ||||||
| Feeling Cold | 0/22 (0%) | 0/24 (0%) | 1/24 (4.2%) | 0/24 (0%) | 9/92 (9.8%) | 8/92 (8.7%) | ||||||
| Local Swelling | 0/22 (0%) | 1/24 (4.2%) | 0/24 (0%) | 0/24 (0%) | 6/92 (6.5%) | 5/92 (5.4%) | ||||||
| Infections and infestations | ||||||||||||
| Cellulitis | 2/22 (9.1%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 0/92 (0%) | 1/92 (1.1%) | ||||||
| Injury, poisoning and procedural complications | ||||||||||||
| Procedural Hypotension | 2/22 (9.1%) | 2/24 (8.3%) | 3/24 (12.5%) | 0/24 (0%) | 10/92 (10.9%) | 6/92 (6.5%) | ||||||
| Wound Dehiscence | 2/22 (9.1%) | 0/24 (0%) | 0/24 (0%) | 1/24 (4.2%) | 2/92 (2.2%) | 0/92 (0%) | ||||||
| Anemia Postoperative | 0/22 (0%) | 0/24 (0%) | 1/24 (4.2%) | 0/24 (0%) | 6/92 (6.5%) | 9/92 (9.8%) | ||||||
| Investigations | ||||||||||||
| Body Temperature Increased | 0/22 (0%) | 0/24 (0%) | 2/24 (8.3%) | 0/24 (0%) | 6/92 (6.5%) | 4/92 (4.3%) | ||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Mobility Decreased | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 6/92 (6.5%) | 5/92 (5.4%) | ||||||
| Nervous system disorders | ||||||||||||
| Dizziness | 3/22 (13.6%) | 3/24 (12.5%) | 4/24 (16.7%) | 6/24 (25%) | 15/92 (16.3%) | 19/92 (20.7%) | ||||||
| Headache | 1/22 (4.5%) | 3/24 (12.5%) | 2/24 (8.3%) | 1/24 (4.2%) | 5/92 (5.4%) | 4/92 (4.3%) | ||||||
| Tremor | 0/22 (0%) | 0/24 (0%) | 0/24 (0%) | 2/24 (8.3%) | 0/92 (0%) | 0/92 (0%) | ||||||
| Psychiatric disorders | ||||||||||||
| Insomnia | 1/22 (4.5%) | 2/24 (8.3%) | 2/24 (8.3%) | 4/24 (16.7%) | 5/92 (5.4%) | 11/92 (12%) | ||||||
| Confusional State | 1/22 (4.5%) | 2/24 (8.3%) | 0/24 (0%) | 0/24 (0%) | 3/92 (3.3%) | 3/92 (3.3%) | ||||||
| Renal and urinary disorders | ||||||||||||
| Urinary Retention | 1/22 (4.5%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 12/92 (13%) | 6/92 (6.5%) | ||||||
| Skin and subcutaneous tissue disorders | ||||||||||||
| Pruritis | 1/22 (4.5%) | 2/24 (8.3%) | 2/24 (8.3%) | 2/24 (8.3%) | 33/92 (35.9%) | 31/92 (33.7%) | ||||||
| Pruritis Generalized | 0/22 (0%) | 1/24 (4.2%) | 0/24 (0%) | 3/24 (12.5%) | 2/92 (2.2%) | 2/92 (2.2%) | ||||||
| Hyperhidrosis | 0/22 (0%) | 0/24 (0%) | 1/24 (4.2%) | 1/24 (4.2%) | 10/92 (10.9%) | 11/92 (12%) | ||||||
| Vascular disorders | ||||||||||||
| Hypertension | 1/22 (4.5%) | 0/24 (0%) | 0/24 (0%) | 2/24 (8.3%) | 3/92 (3.3%) | 6/92 (6.5%) | ||||||
| Hypotension | 1/22 (4.5%) | 2/24 (8.3%) | 0/24 (0%) | 0/24 (0%) | 3/92 (3.3%) | 8/92 (8.7%) | ||||||
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 | 1-855-793-9727 |
| MedInfo@pacira.com |
Responsible Party:
Pacira Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01683071
Other Study ID Numbers:
- 402-C-323
First Posted:
Sep 11, 2012
Last Update Posted:
Dec 9, 2020
Last Verified:
Nov 1, 2020