The study aims to test the safety and effectiveness of two different surgeon-administered methods of the anesthesia medication EXPAREL during knee replacement surgery. This study will not determine whether one method is better than the other, but will instead help the study investigator decide if both methods can provide an equal amount of pain relief.

The main question this study aims to answer is:

Will EXPAREL provide an equal amount of pain relief for patients who receive EXPAREL via Intra-articular Posteromedial Surgeon Administered (IPSA) Block and patients that receive EXPAREL via Local Infiltration Analgesia (LIA)?

Following their surgery, participants will be asked to report their pain level on their treated knee using a numerical rating scale (NRS) between 0 to 10. In addition to their pain level, participants will report any medications used for pain relief and will mark specific regions on an image to indicate where they experience pain.

Inclusion Criteria:

• 18 years of age or older
• Scheduled to undergo total knee arthroplasty (TKA) under spinal anesthesia
• Primary indication for TKA is degenerative osteoarthritis of the knee
• Able to provide informed consent, adhere to the study schedule, and complete all study assessments
• Body Mass Index (BMI) ≥18 and <40 kg/m2

Exclusion Criteria:

• Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (e.g., amide-type local anesthetics, opioids, bupivacaine HCl, NSAIDs)
• Planned concurrent surgical procedure
• Undergoing knee surgery for a single area of the knee or a revision surgery
• History of knee replacement surgery within the past 6 months
• History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years
• Previous participation in an EXPAREL study
• Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, could interfere with study assessments or compliance
• Currently pregnant, nursing, or planning to become pregnant during the study
• Any individual who, per standard of care, is excluded from the surgery due to possibility of pregnancy.
• Male participant in a sexually active relation with pregnant or breastfeeding partner
• Clinically significant medical disease that, in the opinion of the Investigator, would make participation in a clinical study inappropriate.
• Any use of marijuana [including Tetrahydrocannabinol (THC) and Cannabidiol (CBD)] within 30 days prior to randomization, or planned use during the course of the study
• Chronic opioid use within 30 days prior to surgery

All de-identified IPD related to the study protocol will be shared.

IPD will be available between April 1, 2026 until the end of the study.

Access to individual participant data will be limited to collaborators (ie, Pacira) collaborating as defined in the collaborative agreement. De-identified or coded data will be shared solely for analyses related to the objectives of the study. Data will not be made publicly available or shared with external third parties.