Phase 3, Sciatic Nerve Block With EXPAREL for Subjects Undergoing Bunionectomy

This is a Phase 3, multicenter, randomized, double-blind, active controlled study in approximately 180 subjects undergoing bunionectomy. The study will be conducted in two parts (Part A and Part B). Part A will be completed and analyzed before enrollment in Part B is initiated.

Subjects may be screened up to 45 days prior to the day of surgery but eligibility must be re-confirmed on the day of surgery prior to randomization.

The following screening procedures will be performed after the informed consent form (ICF) is signed (if not standard of care): assess eligibility, record medical/surgical history, record prior and concomitant medications, record demographics and baseline characteristics, record subject height and weight for body mass index (BMI) calculation, assess chronic opioid use in the past 30 days, conduct urine pregnancy test for women of childbearing potential, perform 12-lead EKG, record serious adverse events (SAEs) starting when the ICF is signed, and record medications for treatment of SAEs.

On Day 1, prior to sciatic nerve block, study staff will review Pain Rating Guide with the subject and record their responses to:

* Numeric rating scale (NRS) score on the worst pain of their operative foot in the last 30 days. * NRS score on the average pain of their operative foot in the last 30 days.

Part A will enroll approximately 60 subjects undergoing bunionectomy into 1 of 3 arms. They will be randomized 1:1:1 to either EXPAREL 266 mg, EXPAREL 133 mg, or 0.25% bupivacaine HCl (50mg). Part A subjects will be asked to perform sensory function assessments, perform motor function assessments and obtain PK samples. Based on the findings of the interim analysis after completion of Part A, the study may stop for futility or proceed to Part B. Part B is a 2-arm study with 120 subjects being randomized 1:1 to either the better performing dosage of EXPAREL from Part A (266mg or 133mg) or 0.25% bupivacaine HCl (50mg).

All eligible subjects will receive Celecoxib 200 mg, orally (PO) pre-operatively within four hours prior to surgery.

Part A: On Day 1, Subjects will be randomized (1:1:1) to receive a sciatic (in the popliteal fossa) nerve block with a single dose of either: EXPAREL 266 mg, EXPAREL 133 mg, or 0.25% bupivacaine HCl (50 mg).

Part B: will continue enrolling with one of the EXPAREL arms (EXPAREL 266 mg arm or EXPAREL 133 mg arm) and the bupivacaine HCl arm. Therefore, the EXPAREL study arm that fails to show efficacy (conditional power less than 30% in the Part A analysis) will be dropped and the study will continue with two study arms. The final analysis will include subjects from both Part A and Part B.