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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02255500

Enrollment

Registered

2014-10-02

Start date

2014-09-30

Completion date

2015-03-31

Last updated

2021-03-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pain

Keywords

Total knee arthroplasty

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).

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.

Interventions

DRUGBupivacaine 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.

DRUGEXPAREL 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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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: 12. 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.

Design outcomes

Primary

Measure	Time frame	Description
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
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
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
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
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
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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Bupivacaine FNB + EXPAREL Infiltration 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.	16
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.	7
Total	23

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Bupivacaine FNB + EXPAREL Infiltration	Total	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine
Age, Continuous	67.1 years STANDARD_DEVIATION 8.61	64.9 years STANDARD_DEVIATION 8.7	59.7 years STANDARD_DEVIATION 7.04
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	3 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants	20 Participants	7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	.0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	15 Participants	21 Participants	6 Participants
Region of Enrollment United States	16 participants	23 participants	7 participants
Sex: Female, Male Female	9 Participants	13 Participants	4 Participants
Sex: Female, Male Male	7 Participants	10 Participants	3 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 16	0 / 7
other Total, other adverse events	1 / 16	0 / 7
serious Total, serious adverse events	0 / 16	0 / 7

Outcome results

Primary

Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity After Drug Administration (AUC0-∞)

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