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

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.

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.