EXPAREL Infiltration in Subjects Undergoing Femoral Nerve Block With Bupivacaine HCl for Total Knee Arthroplasty

• Sponsor: Pacira Pharmaceuticals, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02255500
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arm: 1
• Duration (Months): 5.9
• Patients Per Site Per Month: 3.9

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and pharmacokinetics of EXPAREL in subjects who undergo femoral nerve block with bupivacaine HCl for unilateral total knee arthroplasty (TKA).

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: Bupivacaine FNB; Drug: EXPAREL Infiltration	Phase 4

Detailed Description

On Day 1, eligible subjects will receive a single 20 mL dose of bupivacaine hydrochloride (HCl) 0.5% with epinephrine 1:200,000 within 2 hours prior to the surgical procedure as an ultrasound-guided femoral nerve block (FNB). EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site prior to wound closure. There will be no local coadministration of the two drugs.

Blood samples for bupivacaine pharmacokinetic (PK) analysis will 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 after the beginning of EXPAREL administration, and on Day 14.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Pharmacokinetics and Safety of Local Administration of EXPAREL in Subjects Undergoing Femoral Nerve Block With Bupivacaine HCl for Unilateral Total Knee Arthroplasty
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Bupivacaine FNB + EXPAREL Infiltration Femoral nerve block 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.

Drug: 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.; Other Names: Bupivacaine ; Drug: 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.; Other Names: Liposomal bupivacaine

Outcome Measures

Primary Outcome Measures

1. Maximum Plasma Concentration (Cmax) [Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose]

   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

2. Time to Peak Plasma Concentration (Tmax) [Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose]

   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

3. Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Drug Administration (AUC0-last) [Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose]

   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

4. Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity After Drug Administration (AUC0-∞) [Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose]

   Total 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

5. The Apparent Terminal Elimination Rate Constant (λz) [Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose]

   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

6. The Apparent Terminal Elimination Half-life (t1/2el) [Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males or females ≥18 years of age.

2. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.

3. Scheduled to undergo femoral nerve block in conjunction with unilateral TKA.

4. Female subjects must be surgically sterile, at least 2 years postmenopausal, or using a medically acceptable method of birth control. Females of childbearing potential must have a documented negative blood or urine pregnancy test result within 24 hours before surgery.

5. Able to provide informed consent, adhere to the study schedule, and complete all study assessments.

Exclusion Criteria:

1. History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics or opioids.

2. Contraindication to bupivacaine.

3. Received bupivacaine or any other local anesthetic within 7 days of EXPAREL administration.

4. Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after EXPAREL administration.

5. Planned concurrent surgical procedure (e.g., bilateral TKA).

6. Body weight <50 kg (110 pounds) or a body mass index ≥45 kg/m2.

7. Received any investigational drug within 30 days prior to EXPAREL administration, and/or has planned administration of another investigational product or procedure during the subject's participation in this study.

8. Previous participation in an EXPAREL study.

9. 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.

10. 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.

11. Clinically significant medical or psychiatric disease that, in the opinion of the Investigator, would constitute a contraindication to participation in the study, or cause inability to comply with the study requirements.

In addition, the subject will be ineligible to receive EXPAREL if he or she meets the following criteria during surgery:

1. Any clinically significant event or condition uncovered during the surgery (e.g., excessive bleeding, acute sepsis) that might render the subject medically unstable or complicate the subject's postsurgical course.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Concepts, GP, LLC	Houston	Texas	United States	77054

Sponsors and Collaborators

• Pacira Pharmaceuticals, Inc

Investigators

• Principal Investigator: David Leiman, MD, Research Concepts, GP, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pacira Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT02255500
• Other Study ID Numbers: 402-C-406
• First Posted: Oct 2, 2014
• Last Update Posted: Mar 8, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by Pacira Pharmaceuticals, Inc: Total knee arthroplasty
• Additional relevant MeSH terms: Bupivacaine

Study Results

Participant Flow

Arm/Group Title	Bupivacaine FNB + EXPAREL Infiltration	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
Arm/Group Description	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.	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."
Period Title: Overall Study
STARTED	16	7
COMPLETED	15	7
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Bupivacaine FNB + EXPAREL Infiltration	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	16	7	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.1 (8.61)	59.7 (7.04)	64.9 (8.7)
Sex: Female, Male (Count of Participants)
Female	9 56.3%	4 57.1%	13 56.5%
Male	7 43.8%	3 42.9%	10 43.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 18.8%	0 0%	3 13%
Not Hispanic or Latino	13 81.3%	7 100%	20 87%
Unknown or Not Reported	0 0%	.0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 6.3%	1 14.3%	2 8.7%
White	15 93.8%	6 85.7%	21 91.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%	7 100%	23 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Plasma Concentration (Cmax)
Description	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
Time Frame	Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bupivacaine FNB + EXPAREL Infiltration	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
Arm/Group Description	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.	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."
Measure Participants	14	7
Mean (Standard Deviation) [ng/mL]	499 (148)	775 (299)

2. Primary Outcome

Title	Time to Peak Plasma Concentration (Tmax)
Description	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
Time Frame	Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bupivacaine FNB + EXPAREL Infiltration	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
Arm/Group Description	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.	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."
Measure Participants	14	7
Median (Full Range) [hours]	0.675	47.450

3. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Drug Administration (AUC0-last)
Description	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
Time Frame	Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bupivacaine FNB + EXPAREL Infiltration	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
Arm/Group Description	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.	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."
Measure Participants	14	7
Mean (Standard Deviation) [hours*ng/mL]	28234 (10710)	46600 (16489)

4. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity After Drug Administration (AUC0-∞)
Description	Total 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
Time Frame	Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupivacaine FNB + EXPAREL Infiltration	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
Arm/Group Description	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.	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."
Measure Participants	6	1
Mean (Standard Deviation) [hours*ng/mL]	25134 (11506)	38489 (NA)

5. Primary Outcome

Title	The Apparent Terminal Elimination Rate Constant (λz)
Description	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
Time Frame	Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bupivacaine FNB + EXPAREL Infiltration	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
Arm/Group Description	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.	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."
Measure Participants	6	1
Mean (Standard Deviation) [1/hours]	0.0290 (0.0089)	.0315 (NA)

6. Primary Outcome

Title	The Apparent Terminal Elimination Half-life (t1/2el)
Description	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
Time Frame	Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bupivacaine FNB + EXPAREL Infiltration	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
Arm/Group Description	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.	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."
Measure Participants	6	1
Mean (Standard Deviation) [hours]	25.9 (8.02)	22 (NA)

Adverse Events

Time Frame	Adverse events were to be monitored from the time the informed consent form was signed through Day 14 post-dose.
Arm/Group Title	Bupivacaine FNB + EXPAREL Infiltration		Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
Arm/Group Description	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.		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.
All Cause Mortality
	Bupivacaine FNB + EXPAREL Infiltration		Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/7 (0%)
Serious Adverse Events
	Bupivacaine FNB + EXPAREL Infiltration		Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Bupivacaine FNB + EXPAREL Infiltration		Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		0/7 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/16 (6.3%)	1	0/7 (0%)	1
Hypercapnia	1/16 (6.3%)	1	0/7 (0%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.