Trial Outcomes & Findings for EXPAREL Infiltration in Subjects Undergoing Femoral Nerve Block With Bupivacaine HCl for Total Knee Arthroplasty (NCT NCT02255500)
NCT ID: NCT02255500
Last Updated: 2021-03-08
Results Overview
The maximum observed plasma concentration of a drug in the body after the drug has been administered. Blood samples for bupivacaine pharmacokinetic (PK) analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
COMPLETED
PHASE4
23 participants
Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
2021-03-08
Participant Flow
Participant milestones
| Measure |
Bupivacaine FNB + EXPAREL Infiltration
Femoral nerve block with bupivacaine hydrochloride (HCl) 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.
|
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from "Bupivacaine FNB + EXPAREL Infiltration."
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
7
|
|
Overall Study
COMPLETED
|
15
|
7
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Bupivacaine FNB + EXPAREL Infiltration
Femoral nerve block with bupivacaine hydrochloride (HCl) 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.
|
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from "Bupivacaine FNB + EXPAREL Infiltration."
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
EXPAREL Infiltration in Subjects Undergoing Femoral Nerve Block With Bupivacaine HCl for Total Knee Arthroplasty
Baseline characteristics by cohort
| Measure |
Bupivacaine FNB + EXPAREL Infiltration
n=16 Participants
FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.
|
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
n=7 Participants
Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from "Bupivacaine FNB + EXPAREL Infiltration."
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
67.1 years
STANDARD_DEVIATION 8.61 • n=5 Participants
|
59.7 years
STANDARD_DEVIATION 7.04 • n=7 Participants
|
64.9 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
.0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
7 participants
n=7 Participants
|
23 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dosePopulation: The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.
The maximum observed plasma concentration of a drug in the body after the drug has been administered. Blood samples for bupivacaine pharmacokinetic (PK) analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Outcome measures
| Measure |
Bupivacaine FNB + EXPAREL Infiltration
n=14 Participants
FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.
|
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
n=7 Participants
Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from "Bupivacaine FNB + EXPAREL Infiltration."
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
499 ng/mL
Standard Deviation 148
|
775 ng/mL
Standard Deviation 299
|
PRIMARY outcome
Timeframe: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dosePopulation: The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.
The time to reach the maximum observed plasma concentration (Cmax) Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Outcome measures
| Measure |
Bupivacaine FNB + EXPAREL Infiltration
n=14 Participants
FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.
|
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
n=7 Participants
Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from "Bupivacaine FNB + EXPAREL Infiltration."
|
|---|---|---|
|
Time to Peak Plasma Concentration (Tmax)
|
0.675 hours
Interval 0.183 to 78.0
|
47.450 hours
Interval 0.183 to 72.9
|
PRIMARY outcome
Timeframe: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dosePopulation: The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.
Total drug exposure up to the last measurable concentration Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Outcome measures
| Measure |
Bupivacaine FNB + EXPAREL Infiltration
n=14 Participants
FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.
|
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
n=7 Participants
Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from "Bupivacaine FNB + EXPAREL Infiltration."
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Drug Administration (AUC0-last)
|
28234 hours*ng/mL
Standard Deviation 10710
|
46600 hours*ng/mL
Standard Deviation 16489
|
PRIMARY outcome
Timeframe: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-doseTotal drug exposure, extrapolated to infinity Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Outcome measures
| Measure |
Bupivacaine FNB + EXPAREL Infiltration
n=6 Participants
FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.
|
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
n=1 Participants
Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from "Bupivacaine FNB + EXPAREL Infiltration."
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity After Drug Administration (AUC0-∞)
|
25134 hours*ng/mL
Standard Deviation 11506
|
38489 hours*ng/mL
Standard Deviation NA
|
PRIMARY outcome
Timeframe: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dosePopulation: The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Outcome measures
| Measure |
Bupivacaine FNB + EXPAREL Infiltration
n=6 Participants
FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.
|
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
n=1 Participants
Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from "Bupivacaine FNB + EXPAREL Infiltration."
|
|---|---|---|
|
The Apparent Terminal Elimination Rate Constant (λz)
|
0.0290 1/hours
Standard Deviation 0.0089
|
.0315 1/hours
Standard Deviation NA
|
PRIMARY outcome
Timeframe: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dosePopulation: The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.
Blood samples for bupivacaine PK analysis were to be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Outcome measures
| Measure |
Bupivacaine FNB + EXPAREL Infiltration
n=6 Participants
FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.
|
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
n=1 Participants
Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.
Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from "Bupivacaine FNB + EXPAREL Infiltration."
|
|---|---|---|
|
The Apparent Terminal Elimination Half-life (t1/2el)
|
25.9 hours
Standard Deviation 8.02
|
22 hours
Standard Deviation NA
|
Adverse Events
Bupivacaine FNB + EXPAREL Infiltration
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Bupivacaine FNB + EXPAREL Infiltration
n=16 participants at risk
FNB with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.
|
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
n=7 participants at risk
Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure.
Bupivacaine FNB: A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
EXPAREL Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 infiltrated into the surgical site just prior to wound closure.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.2%
1/16 • Number of events 1 • Adverse events were to be monitored from the time the informed consent form was signed through Day 14 post-dose.
|
0.00%
0/7 • Adverse events were to be monitored from the time the informed consent form was signed through Day 14 post-dose.
|
|
Respiratory, thoracic and mediastinal disorders
Hypercapnia
|
6.2%
1/16 • Number of events 1 • Adverse events were to be monitored from the time the informed consent form was signed through Day 14 post-dose.
|
0.00%
0/7 • Adverse events were to be monitored from the time the informed consent form was signed through Day 14 post-dose.
|
Additional Information
Pacira Medical Information
Pacira Pharmaceuticals, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place