Efficacy, Safety, and Pharmacokinetics of Femoral Nerve Block With EXPAREL in Total Knee Arthroplasty
Condition: Pain
Intervention: bupivacaine liposome injectable suspension; Placebo
Intervention description: bupivacaine liposome injectable suspension 133 mg expanded with normal saline to 20 mL or 266 mg in 20 mL; Normal saline.
Intervention MeSH terms: Bupivacaine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 232.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study in 232
      adult subjects undergoing primary unilateral TKA under general or spinal anesthesia.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female, at least 18 years of age at screening.

          2. Scheduled to undergo primary unilateral TKA under general or spinal anesthesia.

          3. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.

          4. Female subject must be surgically sterile; or at least 2 years postmenopausal; or have
             a monogamous partner who is surgically sterile; or practicing double-barrier
             contraception; or practicing abstinence (must agree to use double-barrier
             contraception in the event of sexual activity); or using an insertable, injectable,
             transdermal, or combination oral contraceptive approved by the FDA for greater than 2
             months prior to screening and commit to the use of an acceptable form of birth control
             for the duration of the study and for 30 days after completion of the study.

          5. Able to demonstrate sensory function by exhibiting sensitivity to cold, pinprick, and
             light touch.

          6. Able to provide informed consent, adhere to the study visit schedule, and complete all
             study assessments.

        Exclusion Criteria:

          1. Currently pregnant, nursing, or planning to become pregnant during the study or within
             1 month after study drug administration.

          2. Planned concurrent surgical procedure (e.g., bilateral TKA).

          3. Concurrent painful physical condition that may require analgesic treatment (such as an
             NSAID or opioid) in the postsurgical period for pain that is not strictly related to
             the knee surgery and which may confound the postsurgical assessments (e.g.,
             significant pain from other joints including the non-index knee joint, chronic
             neuropathic pain, concurrent or prior contralateral TKA, concurrent foot surgery).

          4. Previous open knee surgery on the knee being considered for TKA. Prior arthroscopy is
             permitted.

          5. History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics.

          6. Contraindication to any one of the following: bupivacaine, oxycodone, morphine, or
             hydromorphone.

          7. Use of any of the following medications within the times specified before surgery:
             long-acting opioid medication or NSAIDs (except for low-dose aspirin used for
             cardioprotection) within 3 days, or any opioid medication within 24 hours.

          8. Initiation of treatment with any of the following medications within 1 month of study
             drug administration or if the medication(s) are being given to control pain: selective
             serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors
             (SNRIs), gabapentin, pregabalin (Lyrica®), or duloxetine (Cymbalta®). If a subject is
             taking one of these medications for a reason other than pain control, he or she must
             be on a stable dose for at least 1 month prior to study drug administration.

          9. Current use of systemic glucocorticosteroids within 1 month of enrollment in this
             study.

         10. Use of dexmedetomidine HCl (Precedex®) within 3 days of study drug administration.

         11. History of impaired kidney function, poorly controlled chronic respiratory disease,
             rheumatoid arthritis, coagulopathy, or loss of sensation in extremities.

         12. Impaired kidney function (e.g., serum creatinine level >2 mg/dL [176.8 µmol/L] or
             blood urea nitrogen level >50 mg/dL [17.9 mmol/L]) or impaired liver function (e.g.,
             serum aspartate aminotransferase [AST] level >3 times the upper limit of normal [ULN]
             or serum alanine aminotransferase [ALT] level >3 times the ULN.)

         13. Uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with
             study assessments.

         14. Any chronic neuromuscular deficit effecting the peripheral nerves or muscles of the
             surgical extremity.

         15. Any chronic condition or disease that would compromise neurological or vascular
             assessments.

         16. 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.

         17. Suspected or known history of drug or alcohol abuse within the previous year.

         18. Body weight <50 kg (110 pounds) or a body mass index >44 kg/m2.

         19. Previous participation in an EXPAREL study.

         20. Administration of an investigational drug within 30 days or 5 elimination half-lives
             of such investigational drug, whichever is longer, prior to study drug administration,
             or planned administration of another investigational product or procedure during the
             subject's participation in this study.